Assessment and monitoring of onchocerciasis in Latin America.

PubMed

Rodríguez-Pérez, Mario A; Unnasch, Thomas R; Real-Najarro, Olga

2011-01-01

Onchocerciasis has historically been one of the leading causes of infectious blindness worldwide. It is endemic to tropical regions both in Africa and Latin America and in the Yemen. In Latin America, it is found in 13 foci located in 6 different countries. The epidemiologically most important focus of onchocerciasis in the Americas is located in a region spanning the border between Guatemala and Mexico. However, the Amazonian focus straddling the border of Venezuela and Brazil is larger in overall area because the Yanomami populations are scattered over a very large geographical region. Onchocerciasis is caused by infection with the filarial parasite Onchocerca volvulus. The infection is spread through the bites of an insect vector, black flies of the genus Simulium. In Africa, the major vectors are members of the S. damnosum complex, while numerous species serve as vectors of the parasite in Latin America. Latin America has had a long history of attempts to control onchocerciasis, stretching back almost 100 years. The earliest programmes used a strategy of surgical removal of the adult parasites from affected individuals. However, because many of the adult parasites lodge in undetectable and inaccessible areas of the body, the overall effect of this strategy on the prevalence of infection was relatively minor. In 1988, a new drug, ivermectin, was introduced that effectively killed the larval stage (microfilaria) of the parasite in infected humans. As the microfilaria is both the stage that is transmitted by the vector fly and the cause of most of the pathologies associated with the infection, ivermectin opened up a new strategy for the control of onchocerciasis. Concurrent with the use of ivermectin for the treatment of onchocerciasis, a number of sensitive new diagnostic tools were developed (both serological and nucleic acid based) that provided the efficiency, sensitivity and specificity necessary to monitor the decline and eventual elimination of onchocerciasis as a result of successful control. As a result of these advances, a strategy for the elimination of onchocerciasis was developed, based upon mass distribution of ivermectin to afflicted communities for periods lasting long enough to ensure that the parasite population was placed on the road to local elimination. This strategy has been applied for the past decade to the foci in Latin America by a programme overseen by the Onchocerciasis Elimination Program for the Americas (OEPA). The efforts spearheaded by OEPA have been very successful, eliminating ocular disease caused by O. volvulus, and eliminating and interrupting transmission of the parasite in 8 of the 13 foci in the region. As onchocerciasis approaches elimination in Latin America, several questions still need to be addressed. These include defining an acceptable upper limit for transmission in areas in which transmission is thought to have been suppressed (e.g. what is the maximum value for the upper bound of the 95% confidence interval for transmission rates in areas where transmission is no longer detectable), how to develop strategies for conducting surveillance for recrudescence of infection in areas in which transmission is thought to be interrupted and how to address the problem in areas where the mass distribution of ivermectin seems to be unable to completely eliminate the infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Knowledge, Attitudes and Practices Survey Conducted Three Years after Halting Ivermectin Mass Treatment for Onchocerciasis in Guatemala

PubMed Central

Richards, Frank O.; Klein, Robert E.; de León, Oscar; Mendizábal-Cabrera, Renata; Morales, Alba Lucía; Cama, Vitaliano; Crovella, Carol G.; Díaz Espinoza, Carlos E.; Morales, Zoraida; Sauerbrey, Mauricio; Rizzo, Nidia

2016-01-01

Background Mass drug administration (MDA) with ivermectin for onchocerciasis was provided in Guatemala’s Central Endemic Zone (CEZ) over a 24 year period (1988–2011). Elimination of Onchocerca volvulus transmission was declared in 2015 after a three year post MDA surveillance period (2012–2014) showed no evidence of recrudescence. The purpose of the present study was to evaluate the knowledge, attitudes and practices (KAP) towards onchocerciasis and ivermectin among residents in the post endemic CEZ. A major interest in this study was to determine what community residents thought about the end of the ivermectin MDA program. Methodology/Principal Findings A total of 148 interviews were conducted in November 2014 in four formerly hyperendemic communities using a standard questionnaire on smart phones. The majority (69%) of respondents knew that the MDA program had ended because the disease was no longer present in their communities, but a slight majority (53%) was personally unsure that onchocerciasis had really been eliminated. Sixty-three percent wanted to continue to receive ivermectin because of this uncertainty, or because ivermectin is effective against intestinal worms. Eighty-nine percent of respondents said that they would seek medical attention immediately if a family member had symptoms of onchocerciasis (especially the presence of a nodule), which is a finding very important for ongoing surveillance. Conclusions/Significance Many respondents wanted to continue receive ivermectin and more than half did not believe onchocerciasis had been eliminated. The ministry of health outreach services should be prepared to address ongoing concerns about onchocerciasis in the post endemic CEZ. PMID:27341104

Mectizan(®) procurement and delivery for onchocerciasis mass drug administration programmes.

PubMed

Ogoussan, Kisito T; Hopkins, Adrian

2011-09-01

The discovery of Mectizan has engendered a safe onchocerciasis chemoprevention tool. To make the drug available promptly to people at risk of onchocerciasis, a procurement and delivery mechanism has been put in place around the Mectizan Donation Program, which oversees the Merck donation of Mectizan. The number of yearly approved treatment doses has increased rapidly since 1988 from 255,000 to more than 80 million in 2007 and 2008. Cumulatively, from 1987 to 2008 more than 697 million treatment doses have been approved corresponding to 1.5 billion Mectizan tablets shipped. Although the current demand for treatment is met, the ultimate goal is to cover all people at risk. A comprehensive drug policy from recipient countries is still needed to back up the current efficient procurement and delivery mechanism in order to attain the ultimate to goal, and is equally important for scaling up mass drug administration as part of national neglected tropical disease control/elimination strategies. Copyright © 2010 Elsevier B.V. All rights reserved.

[Preliminary activities of the program for the control and treatment of onchocerciasis in the Yanomâmi territory, Roraima, Brazil].

PubMed

Coelho, G E; Vieira, J B; Oliveira, C E; Francisco, D A; Pinheiro, L R

1997-01-01

After to characterize the clinic and epidemiological picture of the onchocerciasis in Yanomâmi region, RR, Brazil, begun in 1993, the National Health Foundation (FNS) implemented a Control and Treatment Pilot Project in Tootobi and Balawaú. Here, it was studied skin biopsies from 426 inhabitants. In the nodules of 86.7% from patients was encountered Onchocerca volvulus. The over-all prevalence in the examined population was 66.2%. The treatment with ivermectin covered 80.1% of total population. Adverse reactions, light and moderate, of the medicament were reported in 12.3% of the patients. These results agreeing with the medical literature and suggesting the viability of to increase of the programme for all Yanomâmi area in the next phase.

Impact of Six Years Community Directed Treatment with Ivermectin in the Control of Onchocerciasis, Western Ethiopia

PubMed Central

Samuel, Abdi; Belay, Tariku; Yehalaw, Delenasaw; Taha, Mohammed; Zemene, Endalew; Zeynudin, Ahmed

2016-01-01

Background The African Program for Onchocerciais Control (APOC) with a main strategy of community directed treatment with ivermectin (CDTI) was established with the aim of eliminating Onchocerciasis as a disease of public health and socio-economic importance. The study area was a hyper endemic area just before the implementation of CDTI. It has been implemented for six years in this district but yet not been evaluated. So, the objective of this study was to evaluate the impact of six years CDTI on parasitological and clinical indices of Onchocerciasis Methods This study employed a pre-post impact evaluation design. The minimum sample size for this study was 1318; the respondents were selected by multi-stage sampling technique. Data on socio-demographic characteristics using a semi-structured questionnaire, clinical examination for skin signs and symptoms of Onchocerciasis and two bloodless skin snips from each side of the gluteal fold were taken from the entire study participants. SPSS version 16.0 and Medcalc version 12.2.1.0 were used for analysis. Result The microfilaridermia reduced from the pre-intervention value of 74.8% to 40.7%, indicating a 45.6% reduction, mean intensity from 32.1(SD = 61.5) mf/mg skin snip to 18.7(SD = 28.7)indicating 41.75% reduction, CMFL from 19.6 mf/mg skin snip to 4.7 indicating 76% reduction. The result also showed that microfilaridermia and mean intensity decreased as the number of treatment taken increased. Pruritis, leopard skin, onchocercomata and hanging groin reduced by 54.4%, 61.3%, 77.7% and 88.5% respectively. Conclusions The implementation of CDTI significantly reduced the parasitological and clinical indices of Onchocerciasis, so, efforts should be made to improve the annual treatment coverage and sustainability of CDTI to drastically reduce the micro filarial load to the level the disease would no longer be a public health problem. PMID:26942910

[The effect of ivermectin on geohelminth frequency (i.e. as used in the onchocerciasis control program in Colombia)].

PubMed

Knudson, Angélica; Ariza, Yoseth; López, Myriam C; Fajardo, Oscar S; Reyes, Patricia; Moncada, Ligia I; Duque, Sofía; Álvarez, Carlos A; Nicholls, Rubén S

2012-08-01

Evaluating the effect of ivermectin on soil-transmitted helminthes (STH) infection frequency in a Colombian population included in the Onchocerciasis Elimination Program for the Americas (OEPA). This was an impact evaluation study which adopted a longitudinal approach using the population of Naicioná (1996) as baseline for comparison to people from the same population as controls (2008). The cross-sectional approach involved comparing the reference population of Naicioná (2008) to the population of Dos Quebradas (2008) used as controls. Fecal samples were processed by a modified Ritchie-Frick method. Ascaris lumbricoides was the most frequently found parasite in Naicioná (60/121; 49.6 %: 37.8-63.895%CI) and in Dos Quebradas (36/76; 47.4 %: 33.2-65.6 95 % CI). Ivermectin's main effect on the population aged over 5 years was a decreased risk of Trichiuris trichiura infection in both longitudinal assessment (86 % reduction: 74-93 95 % CI) and cross-sectional assessment (63 %:24-82 95 % CI). A 93 % reduction (45-99 95 % CI) in Strongyloides stercoralis frequency was found in longitudinal assessment, compared to 85 % in cross-sectional assessment (-031-99 95 % CI). Ivermectin use in the OEPA is not sufficient for STH morbidity control. Integrated programs including education and basic sanitation are required.

Onchocerciasis control in the Democratic Republic of Congo (DRC): challenges in a post-war environment.

PubMed

Makenga Bof, J-C; Maketa, V; Bakajika, D K; Ntumba, F; Mpunga, D; Murdoch, M E; Hopkins, A; Noma, M M; Zouré, H; Tekle, A H; Katabarwa, M N; Lutumba, P

2015-01-01

To evaluate onchocerciasis control activities in the Democratic Republic of Congo (DRC) in the first 12 years of community-directed treatment with ivermectin (CDTI). Data from the National Programme for Onchocerciasis (NPO) provided by the National Onchocerciasis Task Force (NOTF) through the annual reports of the 21 CDTI projects for the years 2001-2012 were reviewed retrospectively. A hypothetical-inputs-process-outputs-outcomes table was constructed. Community-directed treatment with ivermectin expanded from 1968 communities in 2001 to 39 100 communities by 2012 while the number of community-directed distributors (CDD) and health workers (HW) multiplied. By 2012, there were ratios of 1 CDD per 262 persons and 1 HW per 2318 persons at risk. More than 80% of the funding came from the fiduciary funds of the African Programme for Onchocerciasis Control. The cost of treatment per person treated fell from US$ 1.1 in 2001 to US$ 0.1 in 2012. The therapeutic coverage increased from 2.7% (2001) to 74.2% (2012); the geographical coverage, from 4.7% (2001) to 93.9% (2012). Geographical coverage fell in 2005 due to deaths in loiasis co-endemic areas, and the therapeutic coverage fell in 2008 due to insecurity. Challenges to CDTI in DRC have been serious adverse reactions to ivermectin in loiasis co-endemic areas and political conflict. Targets for personnel or therapeutic and geographical coverages were not met. Longer term funding and renewed efforts are required to achieve control and elimination of onchocerciasis in DRC. © 2014 John Wiley & Sons Ltd.

Beyond providing drugs: the Mectizan® donation stimulates new strategies in service delivery and in strengthening health systems.

PubMed

Hopkins, Adrian

2012-05-01

The donation of Mectizan® by Merck & Co Inc. in 1987 "as much as was needed for as long as was needed for onchocerciasis control" was a major change from traditional corporate drug donations. The company realised that those who needed the drug most would never be able to purchase it, and so gave it away. The donation enabled the Onchocerciasis Control Programme in West Africa to add Mectizan distribution to its ongoing control strategy. For the first time there was hope for those living in other areas of Africa, Latin America and Yemen. Governments and non-governmental development organizations quickly got together to begin treatment in these new areas. Two new programmes and partnerships were created; the African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas. These programmes have been in the forefront of developing new strategies, including the Community Directed approach, which has now expanded into other disease control programmes at the community level, such as Vitamin A distribution and malaria control. This donation has led not only to the probability of elimination of onchocerciasis in the Americas in the near future, but is stimulating approaches to the elimination in Africa, in areas considered impossible five years ago. Other major pharmaceutical donations have followed, initiating the plan to eliminate lymphatic filariasis worldwide, and also stimulating interest in controlling other "neglected tropical diseases," which affect the poorest billion of the world's population, making this now a reality.

High prevalence of epilepsy in onchocerciasis endemic regions in the Democratic Republic of the Congo

PubMed Central

Tepage, Floribert; Ensoy-Musoro, Chellafe; Mandro, Michel; Bonareri Osoro, Caroline; Suykerbuyk, Patrick; Kashama, Jean Marie; Komba, Michel; Tagoto, Alliance; Falay, Dadi; Begon, Michael

2017-01-01

Background An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. The objective of this study was to determine the prevalence of epilepsy in onchocerciasis endemic areas in the Democratic Republic of the Congo (DRC) and investigate whether a higher annual intake of Ivermectin was associated with a lower prevalence of epilepsy. Methodology/Principle findings Between July 2014 and February 2016, house-to-house epilepsy prevalence surveys were carried out in areas with a high level of onchocerciasis endemicity: 3 localities in the Bas-Uele, 24 in the Tshopo and 21 in the Ituri province. Ivermectin uptake was recorded for every household member. This database allowed a matched case-control pair subset to be created that enabled putative risk factors for epilepsy to be tested using univariate logistic regression models. Risk factors relating to onchocerciasis were tested using a multivariate random effects model. To identify presence of clusters of epilepsy cases, the Kulldorff's scan statistic was used. Of 12, 408 people examined in the different health areas 407 (3.3%) were found to have a history of epilepsy. A high prevalence of epilepsy was observed in health areas in the 3 provinces: 6.8–8.5% in Bas-Uele, 0.8–7.4% in Tshopo and 3.6–6.2% in Ituri. Median age of epilepsy onset was 9 years, and the modal age 12 years. The case control analysis demonstrated that before the appearance of epilepsy, compared to the same life period in controls, persons with epilepsy were around two times less likely (OR: 0.52; 95%CI: (0.28, 0.98)) to have taken Ivermectin than controls. After the appearance of epilepsy, there was no difference of Ivermectin intake between cases and controls. Only in Ituri, a significant cluster (p-value = 0.0001) was identified located around the Draju sample site area. Conclusions The prevalence of epilepsy in health areas in onchocerciasis endemic regions in the DRC was 2–10 times higher than in non-onchocerciasis endemic regions in Africa. Our data suggests that Ivermectin protects against epilepsy in an onchocerciasis endemic region. However, a prospective population based intervention study is needed to confirm this. PMID:28708828

Identification of Human Semiochemicals Attractive to the Major Vectors of Onchocerciasis

PubMed Central

Young, Ryan M.; Burkett-Cadena, Nathan D.; McGaha, Tommy W.; Rodriguez-Perez, Mario A.; Toé, Laurent D.; Adeleke, Monsuru A.; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R.; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L.; Salinas-Carmona, Mario C.; Baker, Bill; Unnasch, Thomas R.; Cupp, Eddie W.

2015-01-01

Background Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Methodology/Principal Findings Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. Conclusions/Significance The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa. PMID:25569240

Identification of human semiochemicals attractive to the major vectors of onchocerciasis.

PubMed

Young, Ryan M; Burkett-Cadena, Nathan D; McGaha, Tommy W; Rodriguez-Perez, Mario A; Toé, Laurent D; Adeleke, Monsuru A; Sanfo, Moussa; Soungalo, Traore; Katholi, Charles R; Noblet, Raymond; Fadamiro, Henry; Torres-Estrada, Jose L; Salinas-Carmona, Mario C; Baker, Bill; Unnasch, Thomas R; Cupp, Eddie W

2015-01-01

Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.

River Blindness: Mathematical Models for Control and Elimination.

PubMed

Basáñez, M G; Walker, M; Turner, H C; Coffeng, L E; de Vlas, S J; Stolk, W A

2016-01-01

Human onchocerciasis (river blindness) is one of the few neglected tropical diseases (NTDs) whose control strategies have been informed by mathematical modelling. With the change in focus from elimination of the disease burden to elimination of Onchocerca volvulus, much remains to be done to refine, calibrate and validate existing models. Under the impetus of the NTD Modelling Consortium, the teams that developed EPIONCHO and ONCHOSIM have joined forces to compare and improve these frameworks to better assist ongoing elimination efforts. We review their current versions and describe how they are being used to address two key questions: (1) where can onchocerciasis be eliminated with current intervention strategies by 2020/2025? and (2) what alternative/complementary strategies could help to accelerate elimination where (1) cannot be achieved? The control and elimination of onchocerciasis from the African continent is at a crucial crossroad. The African Programme for Onchocerciasis Control closed at the end of 2015, and although a new platform for support and integration of NTD control has been launched, the disease will have to compete with a myriad of other national health priorities at a pivotal time in the road to elimination. However, never before had onchocerciasis control a better arsenal of intervention strategies as well as diagnostics. It is, therefore, timely to present two models of different geneses and modelling traditions as they come together to produce robust decision-support tools. We start by describing the structural and parametric assumptions of EPIONCHO and ONCHOSIM; we continue by summarizing the modelling of current treatment strategies with annual (or biannual) mass ivermectin distribution and introduce a number of alternative strategies, including other microfilaricidal therapies (such as moxidectin), macrofilaricidal (anti-wolbachial) treatments, focal vector control and the possibility of an onchocerciasis vaccine. We conclude by discussing challenges, opportunities and future directions. Copyright © 2016 Elsevier Ltd. All rights reserved.

A study of onchocerciasis with severe skin and eye lesions in a hyperendemic zone in the forest of southwestern Cameroon: clinical, parasitologic, and entomologic findings.

PubMed

Somo, R M; Enyong, P A; Fobi, G; Dinga, J S; Lafleur, C; Agnamey, P; Ngosso, A; Ngolle, E M

1993-01-01

Prior to the initiation of an onchocerciasis control program based on the mass administration of ivermectin in the rain forest of southwestern Cameroon, a preliminary baseline study of the area was conducted. The results of this study showed that onchocerciasis was hyperendemic in the area. Skin symptoms and signs were observed including pruritus (67.4% of the population examined), onchocerca nodules (51.6%), skin depigmentation (18.5%), and hanging groins (5.7%). Except for pruritus, the prevalence of these symptoms increased with age. Of the eyes examined, 44.9% had microfilariae in the anterior chamber, 33.5% had choroidoretinitis, 28.0% had punctate keratitis, 8.3% had papillary abnormalities, and 3.6% had sclerosing keratitis. Vision in 10.5% of the eyes examined was classified as blind or very poor (visual acuity = 0-0.10), in 15.7% as poor (visual acuity = 0.11-0.39), and in 73.8% as good (visual acuity = 0.4-1.00). Unlike previous reports that have linked serious ocular damage mainly to savanna onchocerciasis, the present study showed that forest onchocerciasis also caused significant ocular pathology, including blindness. Parasitologically, positive skin snips were recorded for 92.7% of the persons examined, with both sexes being equally infected. The parasite load, expressed as the geometric mean number of microfilariae per skin snip, was 53.6, and was much higher in males than in females. The flv vector, Simulium squamosum, had a high infection rate of 7.5% infective females in Bakumba and 6.8% infective females in Ngbandi, the two fly-catching points. The transmission potential was 266 infective larvae per person per month in Bakumba and 189 in Ngbandi.

Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci

PubMed Central

Zarroug, Isam M. A.; Hashim, Kamal; Elaagip, Arwa H.; Samy, Abdallah M.; Frah, Ehab A.; ElMubarak, Wigdan A.; Mohamed, Hanan A.; Deran, Tong Chor M.; Aziz, Nabil; Higazi, Tarig B.

2016-01-01

Background The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR) and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs. Methods A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007–2008 and 2009–2010). Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests. Results Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies) than Galabat (8,202 flies). In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month), and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month) while none of flies were collected in August-October (MBR = 0 bites/person/month). In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month) and September 2010 (N = 1,163, MBR = 6,978 bites/person/month), whereas, none appeared in collection from April to June. There was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007–2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (rs = 0.799) and were decreased in Kalasecal (rs = - 0.676), Gumaiza (rs = - 0.585), and Hilat Khateir (rs = - 0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00–18:00), while a bimodal pattern with two peaks (07:00–10:00) and (14:00–18:00) was exhibited in Galabat. Conclusion Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan. PMID:26943668

Simuliidae and their relation to human onchocerciasis in northern Venezuela

PubMed Central

Lewis, D. J.; de Aldecoa, R. Ibáñez

1962-01-01

A study of the vectors of onchocerciasis was carried out in 1961 in northern Venezuela at the request of the Venezuelan Government. This article, based on the report submitted, records various observations made—mainly during the dry season—on the identification and biology of the Simuliidae and on the possibilities of controlling them. Twelve Simulium forms were encountered; special attention was paid to the two common man-biting species; S. exiguum, which was abundant but of uncertain relation to onchocerciasis, and S. metallicum. The authors conclude that S. metallicum is the main or only vector in the area studied, but that S. exiguum might possibly also transmit onchocerciasis in certain places near large streams where it is found in great numbers. PMID:20604129

Population biology of human onchocerciasis.

PubMed Central

Basáñez, M G; Boussinesq, M

1999-01-01

Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology. PMID:10365406

Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection.

PubMed

Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea

2007-05-23

Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Over the period 1990-2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries.

Implementing Preventive Chemotherapy through an Integrated National Neglected Tropical Disease Control Program in Mali

PubMed Central

Dembélé, Massitan; Bamani, Sanoussi; Dembélé, Robert; Traoré, Mamadou O.; Goita, Seydou; Traoré, Mamadou Namory; Sidibe, Abdoul Karim; Sam, Letitia; Tuinsma, Marjon; Toubali, Emily; MacArthur, Chad; Baker, Shawn K.; Zhang, Yaobi

2012-01-01

Background Mali is endemic for all five targeted major neglected tropical diseases (NTDs). As one of the five ‘fast-track’ countries supported with the United States Agency for International Development (USAID) funds, Mali started to integrate the activities of existing disease-specific national control programs on these diseases in 2007. The ultimate objectives are to eliminate lymphatic filariasis, onchocerciasis and trachoma as public health problems and to reduce morbidity caused by schistosomiasis and soil-transmitted helminthiasis through regular treatment to eligible populations, and the specific objectives were to achieve 80% program coverage and 100% geographical coverage yearly. The paper reports on the implementation of the integrated mass drug administration and the lessons learned. Methodology/Principal Findings The integrated control program was led by the Ministry of Health and coordinated by the national NTD Control Program. The drug packages were designed according to the disease endemicity in each district and delivered through various platforms to eligible populations involving the primary health care system. Treatment data were recorded and reported by the community drug distributors. After a pilot implementation of integrated drug delivery in three regions in 2007, the treatment for all five targeted NTDs was steadily scaled up to 100% geographical coverage by 2009, and program coverage has since been maintained at a high level: over 85% for lymphatic filariasis, over 90% for onchocerciasis and soil-transmitted helminthiasis, around 90% in school-age children for schistosomiasis, and 76–97% for trachoma. Around 10 million people have received one or more drug packages each year since 2009. No severe cases of adverse effects were reported. Conclusions/Significance Mali has scaled up the drug treatment to national coverage through integrated drug delivery involving the primary health care system. The successes and lessons learned in Mali can be valuable assets to other countries starting up their own integrated national NTD control programs. PMID:22448294

Case-control Studies on the Relationship between Onchocerciasis and Epilepsy: Systematic Review and Meta-analysis

PubMed Central

Kaiser, Christoph; Pion, Sébastien D. S.; Boussinesq, Michel

2013-01-01

Objective A systematic review and meta-analysis of all available case-control studies on the relationship between onchocerciasis and epilepsy. Because age and level of onchocerciasis endemicity in the area of residence are major determinants for infection, an additional analysis was performed, restricted to studies achieving control of these confounding factors. Data sources Medical databases, the “African Neurology Database, Institute of Neuroepidemiology and Tropical Neurology, Limoges,” reference lists of relevant articles, commercial search engines, up to May 2012. Methods We searched for studies examining infection status with Onchocerca volvulus in persons with epilepsy (PWE) and without epilepsy (PWOE) providing data suitable for the calculation of pooled odds ratios (ORp) and/or standardized mean differences (SMD) using random-effects models. Results Eleven studies providing data of qualitative skin biopsies for diagnosis of onchocerciasis were identified. Combined analysis on the total sample of 876 PWE and 4712 PWOE resulted in an ORp of 2.49 (95% confidence interval (95%CI): 1.61–3.86, p<0.001). When this analysis was restricted to those studies achieving control for age, residence and sex (367 PWE, 624 PWOE), an ORp of 1.29 (95% CI: 0.93–1.79; p = 0.139) was found. Presence of nodules for diagnosis of onchocerciasis was analyzed in four studies (225 PWE, 189 PWOE; ORp 1.74; 95%CI: 0.94–3.20; p<0.076), including two studies of the restricted analysis (106 PWE, 106 PWOE; ORp 2.81; 95%CI: 1.57–5.00; p<0.001). One study examined quantitative microfilariae counts in patients without preceding microfilaricidal treatment and demonstrated significantly higher counts in PWE than in PWOE. Interpretation Our results strengthen the hypothesis that, in onchocerciasis foci, epilepsy and infection with O. volvulus are associated. Analysis of indicators giving information on infection intensity, namely nodule palpation and quantitative microfilaria count in untreated patients, support the hypothesis that intensity of infection with O. volvulus is involved in the etiology of epilepsy. PMID:23556028

Validation of a remote sensing model to identify Simulium damnosum s.l. breeding sites in Sub-Saharan Africa.

PubMed

Jacob, Benjamin G; Novak, Robert J; Toe, Laurent D; Sanfo, Moussa; Griffith, Daniel A; Lakwo, Thomson L; Habomugisha, Peace; Katabarwa, Moses N; Unnasch, Thomas R

2013-01-01

Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement.

Validation of a Remote Sensing Model to Identify Simulium damnosum s.l. Breeding Sites in Sub-Saharan Africa

PubMed Central

Jacob, Benjamin G.; Novak, Robert J.; Toe, Laurent D.; Sanfo, Moussa; Griffith, Daniel A.; Lakwo, Thomson L.; Habomugisha, Peace; Katabarwa, Moses N.; Unnasch, Thomas R.

2013-01-01

Background Recently, most onchocerciasis control programs have begun to focus on elimination. Developing an effective elimination strategy relies upon accurately mapping the extent of endemic foci. In areas of Africa that suffer from a lack of infrastructure and/or political instability, developing such accurate maps has been difficult. Onchocerciasis foci are localized near breeding sites for the black fly vectors of the infection. The goal of this study was to conduct ground validation studies to evaluate the sensitivity and specificity of a remote sensing model developed to predict S. damnosum s.l. breeding sites. Methodology/Principal Findings Remote sensing images from Togo were analyzed to identify areas containing signature characteristics of S. damnosum s.l. breeding habitat. All 30 sites with the spectral signature were found to contain S. damnosum larvae, while 0/52 other sites judged as likely to contain larvae were found to contain larvae. The model was then used to predict breeding sites in Northern Uganda. This area is hyper-endemic for onchocerciasis, but political instability had precluded mass distribution of ivermectin until 2009. Ground validation revealed that 23/25 sites with the signature contained S. damnosum larvae, while 8/10 sites examined lacking the signature were larvae free. Sites predicted to have larvae contained significantly more larvae than those that lacked the signature. Conclusions/Significance This study suggests that a signature extracted from remote sensing images may be used to predict the location of S. damnosum s.l. breeding sites with a high degree of accuracy. This method should be of assistance in predicting communities at risk for onchocerciasis in areas of Africa where ground-based epidemiological surveys are difficult to implement. PMID:23936571

Report of the first international workshop on onchocerciasis-associated epilepsy.

PubMed

Colebunders, Robert; Mandro, Michel; Njamnshi, Alfred K; Boussinesq, Michel; Hotterbeekx, An; Kamgno, Joseph; O'Neill, Sarah; Hopkins, Adrian; Suykerbuyk, Patrick; Basáñez, Maria-Gloria; Post, Rory J; Pedrique, Belén; Preux, Pierre-Marie; Stolk, Wilma A; Nutman, Thomas B; Idro, Richard

2018-03-22

Recently, several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy (OAE) may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic. On October 12-14 th 2017, the first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium. The workshop was attended by 79 participants from 20 different countries. Recent research findings strongly suggest that O. volvulus is an important contributor to epilepsy, particularly in meso- and hyperendemic areas for onchocerciasis. Infection with O. volvulus is associated with a spectrum of epileptic seizures, mainly generalised tonic-clonic seizures but also atonic neck seizures (nodding), and stunted growth. OAE is characterised by an onset of seizures between the ages of 3-18 years. Multidisciplinary working groups discussed topics such as how to 1) strengthen the evidence for an association between onchocerciasis and epilepsy, 2) determine the burden of disease caused by OAE, 3) prevent OAE, 4) improve the treatment/care for persons with OAE and affected families, 5) identify the pathophysiological mechanism of OAE, and 6) deal with misconceptions, stigma, discrimination and gender violence associated with OAE. An OAE Alliance was created to increase awareness about OAE and its public health importance, stimulate research and disseminate research findings, and create partnerships between OAE researchers, communities, advocacy groups, ministries of health, non-governmental organisations, the pharmaceutical industry and funding organizations. Although the exact pathophysiological mechanism underlying OAE remains unknown, there is increasing evidence that by controlling and eliminating onchocerciasis, OAE will also disappear. Therefore, OAE constitutes an additional argument for strengthening onchocerciasis elimination efforts. Given the high numbers of people with epilepsy in O. volvulus-endemic regions, more advocacy is urgently needed to provide anti-epileptic treatment to improve the quality of life of these individuals and their families.

Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection

PubMed Central

Vieira, Juan Carlos; Cooper, Philip J; Lovato, Raquel; Mancero, Tamara; Rivera, Jorge; Proaño, Roberto; López, Andrea A; Guderian, Ronald H; Guzmán, José Rumbea

2007-01-01

Background Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. Methods A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. Results Over the period 1990–2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. Conclusion The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries. PMID:17521449

Ivermectin Treatment in Patients With Onchocerciasis-Associated Epilepsy: Protocol of a Randomized Clinical Trial

PubMed Central

Mandro, Michel; Mukendi, Deby; Dolo, Housseini; Suykerbuyk, Patrick; Van Oijen, Marieke

2017-01-01

Background Many studies have reported an association between epilepsy, nodding syndrome (NS), and onchocerciasis (river blindness). A high prevalence of epilepsy has been noted particularly in onchocerciasis hyperendemic areas where onchocerciasis is not or insufficiently controlled with mass ivermectin distribution. There is evidence that increasing the coverage of ivermectin reduces the incidence of epilepsy, and anecdotal evidence suggests a reduction in seizure frequency in onchocerciasis-associated epilepsy (OAE) patients who receive ivermectin. Finding an alternative treatment for epilepsy in these patients will have major consequences. Objective The goal of the study is to assess whether ivermectin treatment decreases the frequency of seizures and leads to seizure freedom in OAE patients, including patients with NS. If we are able to demonstrate such an effect, this would strengthen the argument that onchocerciasis is causing epilepsy and therefore we should increase our efforts to eliminate onchocerciasis. Methods We will conduct a randomized clinical trial in the Democratic Republic of Congo to compare seizure freedom in onchocerciasis-infested epilepsy patients who receive immediate ivermectin treatment with delayed (after 4 months) ivermectin treatment. All participants will simultaneously receive antiepilepsy drugs (AEDs) according to local guidelines for epilepsy treatment. The primary endpoint is seizure freedom defined as no seizures during the 4 month of follow-up. Secondary endpoint is significant (>50%) seizure reduction compared to baseline seizure frequency. Reduction of seizures will be compared between ivermectin and nonivermectin arms. Results Start of enrollment is planned for August 2017, and we expect to have enrolled all 110 participants by December 2017. Results are expected in June 2018. Conclusions If ivermectin treatment in addition to AEDs is able to lead to seizure freedom or significantly reduces seizure frequency in OAE patients, this will have major consequences for epilepsy treatment in onchocerciasis-endemic regions. Ivermectin is donated for free and in non Loa-Loa–endemic regions has negligible side effects. Reducing the burden of epilepsy will have a major impact on quality of life and socioeconomic status of families with affected members in Africa. Trial Registration ClinicalTrials.gov NCT03052998; https://clinicaltrials.gov/ct2/show/NCT03052998 (Archived by WebCite at http://www.webcitation.org/6roFVQSG0) PMID:28855148

Socioeconomic consequences of blinding onchocerciasis in west Africa.

PubMed Central

Evans, T. G.

1995-01-01

Onchocerciasis or river blindness, a major cause of irreversible blindness among adults, has been the focus of international disease control efforts for over 20 years in West Africa. This paper employs the international classification of impairment, disability and handicap (ICIDH) to interpret results from a field study to assess the socioeconomic consequences of onchocerciasis in Guinea in 1987. In a sample of 136 blind, 94 visually impaired and 89 well-sighted persons, decreasing visual acuity is strongly associated with mobility, occupational and marital handicaps. Individual, household and disease correlates were explored. The implications of these findings for the ICIDH concept of handicap are discussed with particular emphasis on the need to extend analysis beyond the individual when assessing the socioeconomic consequences of disabling disease. PMID:7554022

Aspects of black-fly control and entomology in the New World in relation to the Simulium problem in Nigeria*

PubMed Central

Crosskey, R. W.

1959-01-01

A general account is given of insecticidal control of black-flies in North and Central America, and the problems are contrasted with those arising in the control of Simulium damnosum Theo. in Nigeria. Some recent biological observations on Canadian black-flies are described, and it is emphasized that these have materially contributed to successful control. It is pointed out that S. damnosum control is being practised in the absence of much fundamental biological knowledge of this pest. Entomological aspects of onchocerciasis in Mexico and Guatemala are discussed, and compared with S. damnosum and its relationship to onchocerciasis in Nigeria. PMID:13813021

Geographical patterns of onchocerciasis in southern Venezuela: relationships between environment and infection prevalence.

PubMed

Botto, C; Escalona, E; Vivas-Martinez, S; Behm, V; Delgado, L; Coronel, P

2005-03-01

Onchocerciasis is a chronic filarial infection transmitted by Simulium flies that has a focal geographical distribution in Latin America. The southern Venezuelan focus has a gradient of endemicity that includes the largest number of hyperendemic communities in the continent, many of them in remote forest and mountainous areas, where it is an important public health problem among the Yanomami indigenous population. The recent introduction of Geographical Information Systems (GIS) tools and a landscape epidemiology approach for study of vector borne diseases is helping to understand relationships between environment and transmission dynamics of onchocerciasis. Striking differences in the transmission dynamics of onchocerciasis between different river courses were detected. A significant relationship between onchocerciasis and temperature was also demonstrated. The geologic substrate, kind of landscape and vegetation seemed also to influence the transmission of onchocerciasis. In the Venezuelan Amazon, different kinds of landscapes associated with distinctive vector species, show different intensities of transmission of onchocerciasis. In this sense, landscape analysis aided by GIS, may prove to be a useful tool for better identification of the spatial distribution of onchocerciasis risk in the Orinoco basin.

Epilepsy in Onchocerciasis Endemic Areas: Systematic Review and Meta-analysis of Population-Based Surveys

PubMed Central

Pion, Sébastien D. S.; Kaiser, Christoph; Boutros-Toni, Fernand; Cournil, Amandine; Taylor, Melanie M.; Meredith, Stefanie E. O.; Stufe, Ansgar; Bertocchi, Ione; Kipp, Walter; Preux, Pierre-Marie; Boussinesq, Michel

2009-01-01

Objective We sought to evaluate the relationship between onchocerciasis prevalence and that of epilepsy using available data collected at community level. Design We conducted a systematic review and meta-regression of available data. Data Sources Electronic and paper records on subject area ever produced up to February 2008. Review Methods We searched for population-based studies reporting on the prevalence of epilepsy in communities for which onchocerciasis prevalence was available or could be estimated. Two authors independently assessed eligibility and study quality and extracted data. The estimation of point prevalence of onchocerciasis was standardized across studies using appropriate correction factors. Variation in epilepsy prevalence was then analyzed as a function of onchocerciasis endemicity using random-effect logistic models. Results Eight studies from west (Benin and Nigeria), central (Cameroon and Central African Republic) and east Africa (Uganda, Tanzania and Burundi) met the criteria for inclusion and analysis. Ninety-one communities with a total population of 79,270 individuals screened for epilepsy were included in the analysis. The prevalence of epilepsy ranged from 0 to 8.7% whereas that of onchocerciasis ranged from 5.2 to 100%. Variation in epilepsy prevalence was consistent with a logistic function of onchocerciasis prevalence, with epilepsy prevalence being increased, on average, by 0.4% for each 10% increase in onchocerciasis prevalence. Conclusion These results give further evidence that onchocerciasis is associated with epilepsy and that the disease burden of onchocerciasis might have to be re-estimated by taking into account this relationship. PMID:19529767

Chemical control of Simulium ochraceum Walker (Diptera: Simuliidae) larvae in an onchocerciasis endemic area of Guatemala.

PubMed

Yamagata, Y; Ochoa, J O; Molina, P A; Sato, H; Uemoto, K; Suzuki, T

1987-09-01

Chemical control against larvae of Simulium ochraceum, the principal vector of onchocerciasis, was carried out from 1979 to 1984 in a 91.3 km2 area of Guatemala where onchocerciasis is endemic. The control operation was divided chronologically into three phases according to the different tactics employed. Phase 1 (1979-1981), using briquettes of fat and detergent containing 10% temephos, was effective only in perennial streams. Phase 2 (1981-1982), which limited the application target to small streams with discharges of 0.1-1 litre/sec, was not effective. Successful control was achieved by Phase 3 (1982-1984), which consisted of fort-nightly applications of 5% temephos water dispersable powder in fixed doses of 24 g (1.2 g active ingredient) to every 50-100 m stretch of all streams with discharge rates of 0.1-50 l/sec. Vector biting rates were reduced by 97.8% in 1982 to 1983 and 97.6% in 1983-1984. The biting density of S. ochraceum at all five stations was reduced to less than 1.9/man/hour, the proposed critical level for long term transmission of onchocerciasis. The biting density of the S. metallicum/horacioi complex was not apparently affected by this operation. Through analysis of the density of S. ochraceum at various distances from the untreated areas, infiltration of the flies was found to be rare, if the distance was beyond 2 km. Fly-round surveys proved to be practical as a surveillance method for detecting larval breeding in untreated or improperly treated streams. The cost for a nation-wide vector control operation was presented.

Progress toward elimination of onchocerciasis in the Americas - 1993-2012.

PubMed

2013-05-24

Onchocerciasis (river blindness) is caused by the parasitic worm Onchocerca volvulus, transmitted to humans by the bite of infected black flies of the genus Simulium, and is characterized by chronic skin disease, severe itching, and eye lesions that can progress to complete blindness. Currently, among approximately 123 million persons at risk for infection in 38 endemic countries, at least 25.7 million are infected, and 1 million are blinded or have severe visual impairment. Periodic, communitywide mass drug administration (MDA) with ivermectin (Mectizan, Merck) prevents eye and skin disease and might interrupt transmission of the infection, depending on the coverage, duration, and frequency of MDA. The Onchocerciasis Elimination Program for the Americas (OEPA) was launched in response to a 1991 resolution of the Pan American Health Organization (PAHO) calling for the elimination of onchocerciasis from the Americas. By the end of 2012, transmission of the infection, judged by surveys following World Health Organization (WHO) guidelines, had been interrupted or eliminated in four of the six endemic countries in the WHO Americas Region. Thus, in 2013, only 4% (23,378) of the 560,911 persons originally at risk in the Americas will be under ivermectin MDA. Active transmission currently is limited to two foci among Yanomami indigenes in adjacent border areas of Venezuela and Brazil.

Identification of the forest strain of Onchocerca volvulus using the polymerase chain reaction technique.

PubMed

Adewale, B; Mafe, M A; Oyerinde, J P O

2005-01-01

Annual mass treatment with ivermectin for 12-15 years in endemic communities is the control strategy adopted by the African Programme for Onchocerciasis Control (APOC) for the control of onchocerciasis in Nigeria. This long-term treatment necessitates the use of Polymerase Chain Reaction (PCR) for the proper identification of the Onchocerca species and strains in endemic areas and also for monitoring recrudescence of infection in areas where infection has been controlled. This study, which forms part of a larger study on transmission of onchocerciasis identifies the Onchocerca volvulus strain in Ondo state using the Polymerase Chain Reaction (PCR) technique. Deoxyribonucleic acid (DNA) was extracted from the adult worm of Onchocerca parasite using the glass bead method of extraction. The repeated sequence family present in the genome of the parasite designated as 0-150bp was amplified by the polymerase chain reaction (PCR). The amplified parasites produced significant products visible as bands in a 2% agarose gel stained with ethidium bromide. Hybridization of the PCR products with specific DNA probe identified the products as forest strain of Onchocerca volvulus. The epidemiological implication of this is that there would be more of the skin lesions and low blindness rate in the area.

Immunisation with a Multivalent, Subunit Vaccine Reduces Patent Infection in a Natural Bovine Model of Onchocerciasis during Intense Field Exposure

PubMed Central

Makepeace, Benjamin L.; Jensen, Siv Aina; Laney, Sandra J.; Nfon, Charles K.; Njongmeta, Leo M.; Tanya, Vincent N.; Williams, Steven A.; Bianco, Albert E.; Trees, Alexander J.

2009-01-01

Human onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is controlled almost exclusively by the drug ivermectin, which prevents pathology by targeting the microfilariae. However, this reliance on a single control tool has led to interest in vaccination as a potentially complementary strategy. Here, we describe the results of a trial in West Africa to evaluate a multivalent, subunit vaccine for onchocerciasis in the naturally evolved host-parasite relationship of Onchocerca ochengi in cattle. Naïve calves, reared in fly-proof accommodation, were immunised with eight recombinant antigens of O. ochengi, administered separately with either Freund's adjuvant or alum. The selected antigens were orthologues of O. volvulus recombinant proteins that had previously been shown to confer protection against filarial larvae in rodent models and, in some cases, were recognised by serum antibodies from putatively immune humans. The vaccine was highly immunogenic, eliciting a mixed IgG isotype response. Four weeks after the final immunisation, vaccinated and adjuvant-treated control calves were exposed to natural parasite transmission by the blackfly vectors in an area of Cameroon hyperendemic for O. ochengi. After 22 months, all the control animals had patent infections (i.e., microfilaridermia), compared with only 58% of vaccinated cattle (P = 0.015). This study indicates that vaccination to prevent patent infection may be an achievable goal in onchocerciasis, reducing both the pathology and transmissibility of the infection. The cattle model has also demonstrated its utility for preclinical vaccine discovery, although much research will be required to achieve the requisite target product profile of a clinical candidate. PMID:19901988

Elimination of African onchocerciasis: modeling the impact of increasing the frequency of ivermectin mass treatment.

PubMed

Coffeng, Luc E; Stolk, Wilma A; Hoerauf, Achim; Habbema, Dik; Bakker, Roel; Hopkins, Adrian D; de Vlas, Sake J

2014-01-01

The African Programme for Onchocerciasis Control (APOC) is currently shifting its focus from morbidity control to elimination of infection. To enhance the likelihood of elimination and speed up its achievement, programs may consider to increase the frequency of ivermectin mass treatment from annual to 6-monthly or even higher. In a computer simulation study, we examined the potential impact of increasing the mass treatment frequency for different settings. With the ONCHOSIM model, we simulated 92,610 scenarios pertaining to different assumptions about transmission conditions, history of mass treatment, the future mass treatment strategy, and ivermectin efficacy. Simulation results were used to determine the minimum remaining program duration and number of treatment rounds required to achieve 99% probability of elimination. Doubling the frequency of treatment from yearly to 6-monthly or 3-monthly was predicted to reduce remaining program duration by about 40% or 60%, respectively. These reductions come at a cost of additional treatment rounds, especially in case of 3-monthly mass treatment. Also, aforementioned reductions are highly dependent on maintained coverage, and could be completely nullified if coverage of mass treatment were to fall in the future. In low coverage settings, increasing treatment coverage is almost just as effective as increasing treatment frequency. We conclude that 6-monthly mass treatment may only be worth the effort in situations where annual treatment is expected to take a long time to achieve elimination in spite of good treatment coverage, e.g. because of unfavorable transmission conditions or because mass treatment started recently.

Elimination of onchocerciasis from Colombia: first proof of concept of river blindness elimination in the world.

PubMed

Nicholls, Rubén Santiago; Duque, Sofía; Olaya, Luz Adriana; López, Myriam Consuelo; Sánchez, Sol Beatriz; Morales, Alba Lucía; Palma, Gloria Inés

2018-04-11

Onchocerciasis is a chronic parasitic infection originally endemic in 13 discrete regional foci distributed among six countries of Latin America (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela). In Colombia, this disease was discovered in 1965 in the Pacific Coast of the country. The National Onchocerciasis Elimination Program was established in 1993 with the aim of eliminating disease morbidity and infection transmission. In 2013, the World Health Organization (WHO) verified Colombia as free of onchocerciasis, becoming the first country in the world to reach such a goal. This report provides the empirical evidence of the elimination of Onchocerca volvulus transmission by Simulium exiguum (s.l.) after 12 years of 6-monthly mass drug administration of Mectizan® (ivermectin) to all the eligible residents living in this endemic area. From 1996 onwards, a biannual community-based mass ivermectin administration programme was implemented, complemented by health education and community participation. In-depth parasitological, serological and entomological surveys were conducted periodically between 1998 and 2007 to evaluate the impact of ivermectin treatment according to the 2001 WHO guidelines. When the interruption of parasite transmission was demonstrated, the drug distribution ceased and a three-year post-treatment surveillance (PTS) period (2008-2010) was initiated. After 23 rounds of treatment, parasitological and ophthalmological assessments showed absence of microfilariae in skin and anterior chamber of the eyes. Serological tests proved lack of antibodies against O. volvulus in children under 10 years-old. A total of 10,500 S. exiguum flies tested by PCR had no L3 infection (infectivity rate = 0.0095%; 95% CI: 0.0029-0.049) during 2004, indicating interruption of parasite transmission. However, biannual ivermectin treatments continued until 2007 followed by a 3-year PTS period at the end of which 13,481 flies were analyzed and no infective flies were found (infectivity rate = 0%; 95% CI: 0.0-0.014). These results fulfilled the WHO criteria for onchocerciasis elimination. Consequently, in 2013 Colombia was verified as free of onchocerciasis, demonstrating that elimination of this neglected tropical disease is an achievable goal and paving the way for an elimination agenda to be followed by other endemic countries in Latin America and Africa.

[Onchocerciasis among Yanomámi Indians].

PubMed

Moraes, M A

1991-01-01

The main features of the Brazilian focus of onchocerciasis are reported. This focus encompasses large areas of the states of Amazonas and Roraima, in the densely forested highlands of Northern Brazil. It is not clear how the local inhabitants, Indians of the group Yanomámi, an isolated group that has lived in the region for centuries, acquired the infection. However, in some of their villages the prevalence rate among adults is as high as 80%. Aspects of the focus, as its origins, manifestations of the illness among the Indians, and the distribution and importance of the recognized vectors of O. volvulus in the region, are reviewed. The author also makes some considerations on the behavior and probable future of the focus, including the possible dissemination of onchocerciasis to some other sites of Brazil. Gold miners that in recent years have invaded the Yanomámi territory and became infected in contact with the Indians will be the cause of this dissemination. Methods for controlling onchocerciasis are discussed and, besides the treatment of the infected Indians with Ivermectin, it is proposed the use of larvicides to eliminate the vectors. This method would be employed in some limited areas where the population is already stable and shows a very high prevalence rate.

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model

PubMed Central

Hess, Jessica A.; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M.; Bottazzi, Maria Elena; Hotez, Peter J.; Klei, Thomas R.; Lustigman, Sara; Abraham, David

2014-01-01

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunization protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. PMID:24907553

Proof-of-principle of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: final results of a study in Mali and Senegal.

PubMed

Traore, Mamadou O; Sarr, Moussa D; Badji, Alioune; Bissan, Yiriba; Diawara, Lamine; Doumbia, Konimba; Goita, Soula F; Konate, Lassana; Mounkoro, Kalifa; Seck, Amadou F; Toe, Laurent; Toure, Seyni; Remme, Jan H F

2012-01-01

Mass treatment with ivermectin controls onchocerciasis as a public health problem, but it was not known if it could also interrupt transmission and eliminate the parasite in endemic foci in Africa where vectors are highly efficient. A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection and transmission, and test whether treatment could be safely stopped. This article reports the results of the final evaluations up to 5 years after the last treatment. Skin snip surveys were undertaken in 131 villages where 29,753 people were examined and 492,600 blackflies were analyzed for the presence of Onchocerca volvulus larva using a specific DNA probe. There was a declining trend in infection and transmission levels after the last treatment. In two sites the prevalence of microfilaria and vector infectivity rate were zero 3 to 4 years after the last treatment. In the third site, where infection levels were comparatively high before stopping treatment, there was also a consistent decline in infection and transmission to very low levels 3 to 5 years after stopping treatment. All infection and transmission indicators were below postulated thresholds for elimination. The study has established the proof of principle that onchocerciasis elimination with ivermectin treatment is feasible in at least some endemic foci in Africa. The study results have been instrumental for the current evolution from onchocerciasis control to elimination in Africa.

RRR for NNN-a rapid research response for the Neglected Tropical Disease NGDO Network: a novel framework to challenges faced by the global programs targeting neglected tropical diseases.

PubMed

Toledo, Chelsea E; Jacobson, Julie; Wainwright, Emily C; Ottesen, Eric A; Lammie, Patrick J

2016-03-01

While global programs targeting the control or elimination of five of the neglected tropical diseases (NTDs)-lymphatic filariasis, onchocerciasis, soil-transmitted helminthiasis, schistosomiasis and trachoma-are well underway, they still face many operational challenges. Because of the urgency of 2020 program targets, the Bill & Melinda Gates Foundation and the U.S. Agency for International Development devised a novel rapid research response (RRR) framework to engage national programs, researchers, implementers and WHO in a Coalition for Operational Research on NTDs. After 2 years, this effort has succeeded as an important basis for the research response to programmatic challenges facing NTD programs. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Eye disease related to onchocerciasis: a clinical study in the Aratha-ú, Yanomami Tribe, Roraima State, Brazil.

PubMed

Neto, Guilherme Herzog; Jaegger, Karen; Marchon-Silva, Verônica; Calvão-Brito, Regina Helena Santos; Vieira, João Batista; Banic, Dalma Maria; Maia-Herzog, Marilza

2009-11-01

The prevalence of ocular lesions due to onchocerciasis was evaluated among residents of the Yanomami Tribe, in the northern Amazon, Brazil, an endemic area for onchocerciasis. 83 natives were submitted to an ocular examination including an external examination, biomicroscopy, intraocular pressure measurement, and a fundus examination. Clinical, parasitological and serological tests were carried out simultaneously. The population demonstrated a high prevalence of eosinophilia, skin microfilaria (55%) and onchocercal subcutaneous nodules (35%). A high prevalence of probable onchocerciasis related eye lesions was detected. Punctate keratitis (41%) and microfilaria in the anterior chamber (39%) were found as well as other probable onchocercotic lesions-chorioretinitis (7.2%) and anterior uveitis (6.0%). Other anterior eye lesions (corneal leucomas, conjunctival injection, lid nodules) occurred in 51% of the individuals. The anterior eye lesions were more prevalent than the posterior lesions. We did not find an association of glaucoma with onchocerciasis. The prevalence of these suggestive ocular lesions strongly correlates with the cutaneous nodules and eosinophilia, suggesting that skin nodules may be an indication for an eye examination. The present study provides evidence that significant infection and eye disease due to onchocerciasis persists in certain regions of Northern South America.

Prediction of community prevalence of human onchocerciasis in the Amazonian onchocerciasis focus: Bayesian approach.

PubMed Central

Carabin, Hélène; Escalona, Marisela; Marshall, Clare; Vivas-Martínez, Sarai; Botto, Carlos; Joseph, Lawrence; Basáñez, María-Gloria

2003-01-01

OBJECTIVE: To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the factors that influence prevalence of microfilariae in the Amazonian focus of onchocerciasis and predict the probability of any community being at least mesoendemic (>20% prevalence of microfilariae), and thus in need of priority ivermectin treatment. METHODS: Models were developed with data from 732 individuals aged > or =15 years who lived in 29 Yanomami communities along four rivers of the south Venezuelan Orinoco basin. The models' abilities to predict prevalences of microfilariae in communities were compared. The deviance information criterion, Bayesian P-values, and residual values were used to select the best model with an approximate cross-validation procedure. FINDINGS: A three-level model that acknowledged clustering of infection within communities performed best, with host age and sex included at the individual level, a river-dependent altitude effect at the community level, and additional clustering of communities along rivers. This model correctly classified 25/29 (86%) villages with respect to their need for priority ivermectin treatment. CONCLUSION: Bayesian methods are a flexible and useful approach for public health research and control planning. Our model acknowledges the clustering of infection within communities, allows investigation of links between individual- or community-specific characteristics and infection, incorporates additional uncertainty due to missing covariate data, and informs policy decisions by predicting the probability that a new community is at least mesoendemic. PMID:12973640

Can ivermectin mass treatments eliminate onchocerciasis in Africa?

PubMed Central

Winnen, M.; Plaisier, A. P.; Alley, E. S.; Nagelkerke, N. J. D.; van Oortmarssen, G.; Boatin, B. A.; Habbema, J. D. F.

2002-01-01

OBJECTIVE: To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. METHODS: ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. FINDINGS: Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. CONCLUSION: Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas. PMID:12077614

Prediction of community prevalence of human onchocerciasis in the Amazonian onchocerciasis focus: Bayesian approach.

PubMed

Carabin, Hélène; Escalona, Marisela; Marshall, Clare; Vivas-Martínez, Sarai; Botto, Carlos; Joseph, Lawrence; Basáñez, María-Gloria

2003-01-01

To develop a Bayesian hierarchical model for human onchocerciasis with which to explore the factors that influence prevalence of microfilariae in the Amazonian focus of onchocerciasis and predict the probability of any community being at least mesoendemic (>20% prevalence of microfilariae), and thus in need of priority ivermectin treatment. Models were developed with data from 732 individuals aged > or =15 years who lived in 29 Yanomami communities along four rivers of the south Venezuelan Orinoco basin. The models' abilities to predict prevalences of microfilariae in communities were compared. The deviance information criterion, Bayesian P-values, and residual values were used to select the best model with an approximate cross-validation procedure. A three-level model that acknowledged clustering of infection within communities performed best, with host age and sex included at the individual level, a river-dependent altitude effect at the community level, and additional clustering of communities along rivers. This model correctly classified 25/29 (86%) villages with respect to their need for priority ivermectin treatment. Bayesian methods are a flexible and useful approach for public health research and control planning. Our model acknowledges the clustering of infection within communities, allows investigation of links between individual- or community-specific characteristics and infection, incorporates additional uncertainty due to missing covariate data, and informs policy decisions by predicting the probability that a new community is at least mesoendemic.

Important progress towards elimination of onchocerciasis in the West Region of Cameroon.

PubMed

Kamga, Guy-Roger; Dissak-Delon, Fanny N; Nana-Djeunga, Hugues C; Biholong, Benjamin D; Ghogomu, Stephen Mbigha; Souopgui, Jacob; Kamgno, Joseph; Robert, Annie

2017-08-03

After more than a decade of community-directed treatment with ivermectin (CDTI) in the West Region of Cameroon, epidemiological evaluation conducted in 2011 showed that onchocerciasis endemicity was still high in some communities. The conceptual framework for onchocerciasis elimination recommends in such case, to conduct additional phase 1A surveys at intervals of three to four years. Therefore, to assess the progress made towards the elimination of onchocerciasis in the West CDTI projects, we conducted a cross-sectional survey in May 2015 in 15 unevaluated communities where the highest baseline endemicity level were found in 1996. All volunteers living for at least five years in the community, aged five years or more, underwent clinical and parasitological examinations. Individual adherence to ivermectin treatment was also assessed. Analyses of data were weighted proportionally to age and gender distribution in the population. The mean age was 28.4 ± 22.2 years and there were 55% of women among the 2058 individuals examined. The weighted prevalences were 5.5%, 2.1% and 1.7% for microfilaridermia, nodule and cutaneous signs, respectively. The weighted microfilaridermia prevalences varied from 4.0 in 5-9 years old to 11.6% in 40-49 years old. In the 30 children under 10 years examined in Makouopsap, the weighted prevalences were 49.9% for microfilaridermia and 13.3% for nodule. In surveyed communities, the weighted prevalences varied from 0 to 41.6% for microfilaridermia, with 11 (73.3%) communities having <5%. Except Makouopsap which had 41.6%, all the surveyed communities were below 15% for microfilaridermia prevalence. The community microfilarial load (CMFL) expressed in microfilariae/skin snip (mf/ss), also significantly dropped by 98-100%, from 3.75-33.16 mf/ss in 1996 to 0-0.94 mf/ss in 2015. The weighted therapeutic coverage in 2014 was 69.4% and the 5 years' adherence was only 39.3% among participants. After more than 15 years of CDTI, there is an important progress towards the elimination of onchocerciasis in the communities surveyed. Innovative strategy like semi-annual ivermectin treatment plus vector control or the adjunction of a vector control strategy to the current annual treatment should be implemented in the bordering districts of the Centre and West Regions, as well as in other parts of the country with persistent high prevalences in the sight of onchocerciasis elimination.

How Can Onchocerciasis Elimination in Africa Be Accelerated? Modeling the Impact of Increased Ivermectin Treatment Frequency and Complementary Vector Control.

PubMed

Verver, Suzanne; Walker, Martin; Kim, Young Eun; Fobi, Grace; Tekle, Afework H; Zouré, Honorat G M; Wanji, Samuel; Boakye, Daniel A; Kuesel, Annette C; de Vlas, Sake J; Boussinesq, Michel; Basáñez, Maria-Gloria; Stolk, Wilma A

2018-06-01

Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Areas with 40%-50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%-80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model.

PubMed

Hess, Jessica A; Zhan, Bin; Bonne-Année, Sandra; Deckman, Jessica M; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David

2014-08-01

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Review of epidemiological studies searching for a relationship between onchocerciasis and epilepsy.

PubMed

Druet-Cabanac, M; Boussinesq, M; Dongmo, L; Farnarier, G; Bouteille, B; Preux, P M

2004-01-01

A review and a meta-analysis of the available epidemiological literature for evidence of an association between onchocerciasis infection and epilepsy were carried out. We used EMBASE (1974-2002), MEDLINE (1966-2002), and PASCAL (1987-2002) databases and relevant journals and bibliographies. We limited our analysis to the epidemiological studies, where the status regarding onchocerciasis infection and epilepsy was available for each subject. Nine African studies were included. The common relative risk estimated by the random-effects model was 1.21 (95% CI 0.99-1.47; p = 0.06). The meta-analysis did not show any difference according to the onchocerciasis endemicity level and the African areas. Our results do not allow to conclude for an association between Onchocerca volvulus infection and epilepsy. However, the results are nearly significant. Further research is needed in this neglected subject, in particular for the better understanding of the neurological pathogenicity in onchocerciasis. Copyright 2004 S. Karger AG, Basel

Drawing and interpreting data: Children's impressions of onchocerciasis and community-directed treatment with ivermectin (CDTI) in four onchocerciasis endemic countries in Africa

PubMed Central

Amuyunzu-Nyamongo, Mary; Tchounkeu, Yolande Flore Longang; Oyugi, Rahel Akumu; Kabali, Asaph Turinde; Okeibunor, Joseph C.; Manianga, Cele; Amazigo, Uche V.

2011-01-01

Although the depiction of a child leading a blind man is the most enduring image of onchocerciasis in Africa, research activities have hardly involved children. This paper aims at giving voice to children through drawings and their interpretation. The study was conducted in 2009 in Cameroon, Democratic Republic of Congo (DRC), Nigeria and Uganda. Children aged 6–16 years were asked to draw their perceptions of onchocerciasis and community-directed treatment with ivermectin (CDTI) in their communities. A total of 50 drawings were generated. The drawings depicted four main aspects of onchocerciasis: (1) the disease symptoms, (2) the negative consequences of onchocerciasis among children and in the community generally, (3) the ivermectin distribution process, and (4) the benefits or effects of taking ivermectin. Out of the 50 drawings, 30 were on symptoms, 7 on effects of the disease on children, 8 on distribution process, and 5 represented multiple perceptions on symptoms, drug distribution processes, benefits, and effects of treatment. The lack of clarity when treatment with ivermectin can be stopped in endemic areas requires working with children to ensure continued compliance with treatment into the future. Children's drawings should be incorporated into health education interventions. PMID:21637349

[Entomologic study on the transmission of onchocerciasis in a forest-savanna transition area of Cameroon].

PubMed

Barbazan, P; Escaffre, H; Mbentengam, R; Boussinesq, M

1998-01-01

An entomological study was conducted in the basin area of middle Sanaga (Cameroon) in order to document the pattern of onchocerciasis transmission in a region where a high prevalence of infection had been recorded in villages located 30 km from the main rivers. The main vector of O. volvulus was found to be S. squamosum s.s. No breeding site was found in the small tributaries of the Sanaga and Mbam Rivers, and the dispersal of S. damnosum s.l. in the area thus appeared to be particularly high. The highest blackfly population densities were recorded during the long rainy season, and a second peak of density occurred along the Mbam River during the short rainy season. A seasonal variation in dispersal patterns was found at three of the four transects studied. The transmission of Onchocerca volvulus in the area occurred principally between January and May (i.e. at the end of the long dry season and the beginning of the short rainy season). Vector control operations might well reinforce the effect of ivermectin distributions in this onchocerciasis focus.

Interruption of onchocerciasis transmission in Bioko Island: Accelerating the movement from control to elimination in Equatorial Guinea

PubMed Central

Garcia, Belén; Ncogo, Policarpo; Perteguer, Maria Jesus; Rubio, Jose Miguel; Rivas, Eva; Cimas, Marta; Ordoñez, Guillermo; de Pablos, Silvia; Hernández-González, Ana; Nguema, Rufino; Moya, Laura; Romay-Barja, María; Garate, Teresa; Barbre, Kira; Benito, Agustín

2018-01-01

Background Onchocerciasis, also known as river blindness, is a parasitic disease. More than 99 percent of all cases occur in Africa. Bioko Island (Equatorial Guinea) is the only island endemic for onchocerciasis in the world. Since 2005, when vector Simulium yahense was eliminated, there have not been any reported cases of infection. This study aimed to demonstrate that updated WHO criteria for stopping mass drug administration (MDA) have been met. Methodology/Principal findings A cross-sectional study was conducted from September 2016 to January 2017. Participants were 5- to 9-year-old school children. Onchocerciasis/lymphatic Filariasis (LF, only in endemic districts) rapid diagnostic tests (RDTs) were performed. Blood spots were collected from RDT positive children and 10 percent of the RDT negatives to determine Ov16 and Wb123 IgG4 antibodies through enzyme-linked immunosorbent assay (ELISA). Skin snips were collected from RDT positives. Filarial detection was performed by PCR in positives and indeterminate sera. Black fly collection was carried out in traditional breeding sites. A total of 7,052 children, ranging from 5 to 9 years of age, were included in the study. Four children (0.06%) were Ov16 IgG4 RDT positives, but negative by ELISA Ov16, while 6 RDT negative children tested positive by ELISA. A total of 1,230 children from the Riaba and Baney districts were tested for LF. One child was Wb123 RDT positive (0.08%), but ELISA negative, while 3 RDT negative children were positive by Wb123 ELISA. All positive samples were negative by PCR for onchocerciasis and LF (in blood spot and skin snip). All fly collections and larval prospections in the traditional catching and prospection sites were negative. Conclusions/Significance WHO criteria have been met, therefore MDA in Bioko Island can be stopped. Three years of post-treatment surveillance should be implemented to identify any new occurrences of exposure or infection. PMID:29723238

Time Series Analysis of Onchocerciasis Data from Mexico: A Trend towards Elimination

PubMed Central

Pérez-Rodríguez, Miguel A.; Adeleke, Monsuru A.; Orozco-Algarra, María E.; Arrendondo-Jiménez, Juan I.; Guo, Xianwu

2013-01-01

Background In Latin America, there are 13 geographically isolated endemic foci distributed among Mexico, Guatemala, Colombia, Venezuela, Brazil and Ecuador. The communities of the three endemic foci found within Mexico have been receiving ivermectin treatment since 1989. In this study, we predicted the trend of occurrence of cases in Mexico by applying time series analysis to monthly onchocerciasis data reported by the Mexican Secretariat of Health between 1988 and 2011 using the software R. Results A total of 15,584 cases were reported in Mexico from 1988 to 2011. The data of onchocerciasis cases are mainly from the main endemic foci of Chiapas and Oaxaca. The last case in Oaxaca was reported in 1998, but new cases were reported in the Chiapas foci up to 2011. Time series analysis performed for the foci in Mexico showed a decreasing trend of the disease over time. The best-fitted models with the smallest Akaike Information Criterion (AIC) were Auto-Regressive Integrated Moving Average (ARIMA) models, which were used to predict the tendency of onchocerciasis cases for two years ahead. According to the ARIMA models predictions, the cases in very low number (below 1) are expected for the disease between 2012 and 2013 in Chiapas, the last endemic region in Mexico. Conclusion The endemic regions of Mexico evolved from high onchocerciasis-endemic states to the interruption of transmission due to the strategies followed by the MSH, based on treatment with ivermectin. The extremely low level of expected cases as predicted by ARIMA models for the next two years suggest that the onchocerciasis is being eliminated in Mexico. To our knowledge, it is the first study utilizing time series for predicting case dynamics of onchocerciasis, which could be used as a benchmark during monitoring and post-treatment surveillance. PMID:23459370

Vision 2020 - the right to sight.

PubMed

Resnikoff, S; Kocur, I; Etya'ale, D E; Ukety, T O

2008-09-01

The unprecedented partnership for onchocerciasis control that followed Merck's decision to donate Mectizan has inspired the formation of a global initiative for the elimination of all avoidable blindness by the year 2020. 'Vision 2020, the Right to Sight', jointly co-ordinated by the World Health Organization's Programme for the Prevention of Blindness and Deafness and the International Agency for the Prevention of Blindness, was launched in 1999. This initiative's three pillars are disease control, human resource development, and infrastructure development. Vision 2020's achievements to date include the growth of the partnership, to include more than 60 member organizations, the revitalization of prevention activities, the completion of Vision-2020 plans in 40% of all countries and a reduction not only of blindness caused by onchocerciasis but also of blindness caused by trachoma. Cataract remains the leading cause of avoidable blindness.

Prospects for the control of onchocerciasis in Africa

PubMed Central

Waddy, B. B.

1969-01-01

Onchocerciasis is found in association with all the main river systems of northern tropical Africa, and there are endemic foci south of the Equator. Heavy and prolonged infection may cause blindness and intense pruritis. The vectors, Simulium damnosum and S. neavei, are also intolerable pests when they swarm. The disease and its vector together cause serious economic loss and are a main cause of the depopulation of river valleys in the savanna lands. The basin of the River Volta, in which the worst endemic area in the world is situated, is considered to be the most favourable area for a study of the problems involved in the large-scale control of onchocerciasis carried by S. damnosum. Mass treatment or prophylaxis are not practicable at present. The clinical condition progresses for many years in the absence of fresh infection, and drugs capable of mass application are needed. However, the first aim is to attack the larval stages of the vector with insecticides. DDT is ideal for this purpose in large, steadily flowing rivers, but a more suitable insecticide and formulation are needed for small, irregularly flowing streams. Research is needed into many aspects of the adult life of S. damnosum, including feeding and resting habits, dry season survival and flight range. One of the main practical problems is prevention of reinfestation of a treated river system. PMID:5307598

Retinoid Expression in Onchocercal Skin Disease: Pilot Study

PubMed Central

Mawson, Anthony R; Makunde, Williams H; Penman, Alan D; Hernandez Morales, Veronica de Los Angeles; Kalinga, Akili K; Francis, Filbert; Rubinchik, Semyon; Kibweja, Addow

2017-01-01

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA (r2 = 0.25, P = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light. PMID:29317828

Retinoid Expression in Onchocercal Skin Disease: Pilot Study.

PubMed

Mawson, Anthony R; Makunde, Williams H; Penman, Alan D; Hernandez Morales, Veronica de Los Angeles; Kalinga, Akili K; Francis, Filbert; Rubinchik, Semyon; Kibweja, Addow

2017-01-01

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA ( r 2  = 0.25, P  = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light.

Human onchocerciasis in the Amazonian area of southern Venezuela: spatial and temporal variations in biting and parity rates of black fly (Diptera: Simuliidae) vectors.

PubMed

Grillet, M E; Basáñez, M G; Vivas-Martínez, S; Villamizar, N; Frontado, H; Cortez, J; Coronel, P; Botto, C

2001-07-01

We investigated some entomological factors underlying altitudinal prevalence variation in the Venezuelan Amazonia human onchocerciasis focus. Spatial and temporal variation in relative abundance, daily biting rate, proportion of parous flies, and monthly parous biting rate were studied for the three main simuliid vectors (based on their vectorial competence: Simulium oyapockense s.l. Floch & Abonnenc approximately = S. incrustatum Lutz < S. guianense s.l. Wise). Yanomami villages were selected among sentinel communities of the ivermectin control program, representing hypo- to hyperendemicity conditions of infection. Spatial variation was explored via increasing village altitude on two river systems (A: Ocamo-Putaco and B: Orinoco-Orinoquito). Temporal variation was studied between 1995 and 1999 by sampling the biting population during dry and rainy mouths. Environmental variables included monthly rainfall and maximum river height. Simuliid species composition itself varied along the altitudinal and prevalence gradient. S. oyapockense s.l. prevailed below 150 m. Above this altitude and up to 240 m, S. incrustatum and S. guianense s.l. became more frequently and evenly collected along A but not along B, where S. incrustatum remained absent. The daily biting rate of S. oyapockense s.l. was higher during the dry season along A, whereas the converse took place along B. Daily biting rate of S. incrustatum was lowest during early rains. By contrast, the daily biting rate of S. guianense s.l. was highest during this period. There was a significant negative cross-correlation between proportion of parous of S. oyapockense s.l. and river height (2 and 3 mo lagged), whereas this variable (1 and 2 mo lagged) was positively correlated with the proportion of parous flies for S. incrustatum. Monthly parous biting rate values suggest that the months contributing most to onchocerciasis transmission in the area are likely to be the dry season and the transition periods between seasons.

Outstanding insecurities concerning the use of an Ov16-based ELISA in the Amazonia onchocerciasis focus.

PubMed

Luz, Sérgio Luiz Bessa; Crainey, James Lee; Shelley, Anthony John; Rubio, Miguel

2014-07-01

In a recent issue of Memórias do Instituto Oswaldo Cruz, published in Rio de Janeiro in February 2014 (109: 87-92), Adami et al. have published a survey reporting Mansonella parasite prevalence in the Amazon Region. This report makes a useful contribution to the existing knowledge of filarial parasite distribution within the Amazon area, parasite prevalence rates in relation to age and occupation and provides observations on the possible clinical impact of Mansonella ozzardi. Their publication also provides an account of what appears to be a novel ELISA that has recently been used in the Simuliidae and Onchocerciasis Laboratory of the Oswaldo Cruz Institute, Rio de Janeiro, Brazil. We are concerned that the publication of this ELISA may have created an excessively positive impression of the effectiveness of the onchocerciasis recrudescence serological surveillance tools that are presently available for use in the Amazonia onchocerciasis focus. In this letter we have, thus, sought to highlight some of the limitations of this ELISA and suggest how continuing insecurities concerning the detection of antibodies to Onchocerca volvulus within the Amazonia onchocerciasis focus might be minimised.

The onchocerciasis chronicle: from the beginning to the end?

PubMed

Crump, Andy; Morel, Carlos M; Omura, Satoshi

2012-07-01

The year 2012 marks the 25th anniversary of the donation of ivermectin to fight onchocerciasis and the projected date for elimination of transmission of the disease in the Americas. This review looks at the history of onchocerciasis, from its discovery through to 2025, by which time it is projected that the disease will have been eliminated as a public health problem, except in a handful of sub-Saharan countries, where it should be well on the way towards elimination. Copyright © 2012 Elsevier Ltd. All rights reserved.

The interruption of Onchocerca volvulus and Wuchereria bancrofti transmission by integrated chemotherapy in the Obongi focus, North Western Uganda

PubMed Central

Gabriel, Matwale; Tukahebwa, Edridah; Onapa, Ambrose Winston; Tinkitina, Benjamin; Tukesiga, Ephraim; Nyaraga, Michael; Auma, Anna Mary; Habomugisha, Peace; Byamukama, Edson; Oguttu, David; Katabarwa, Moses; Unnasch, Thomas Raymond

2017-01-01

Intervention Few studies have documented the interruption of onchocerciasis and Lymphatic Filariasis (LF) by integrated chemotherapy in Uganda. The study describes the interruption of transmission of the two diseases co-endemic in Obongi focus, north western Uganda. Base line data for Onchocerciasis and LF were collected in 1994 and 2006, respectively. Annual mass drug administration for onchocerciasis (Ivermectin) and Lymphatic Filariasis (Ivermectin + albendazole) was conducted for 20 and 6 years, respectively. Thereafter, assessments by skin snip, larval searches in rivers and human landing catches were performed. Children <10 years were screened for IgG4 antibodies using Ov16 ELISA technique in 2013. LF Pre-TAS and TAS1 were conducted in sentinel sites. ITN coverage and utilization for the implementation unit was also reported. Intervention coverage Onchocerciasis treatment coverage was <80% but improved with the introduction of CDTI in 1999. While for LF, effective coverage of >65% was achieved in the six treatment rounds. Household ownership of ITN’s and utilization was 96% and 72.4%., respectively. Impact Parasitological examinations conducted for onchocerciasis among 807 adults and children, revealed a reduction in mf prevalence from 58% in 1994 to 0% in 2012. Entomological monitoring conducted at the two sites had no single Simulium damnosum fly caught. Serological analysis using Ov16 ELISA for onchocerciasis revealed that out of the 3,308 children <10 years old screened in 2013, only 3/3308 (0.091%) positive cases were detected. All Ov16 positive children were negative when tested for patent infection by skin snip PCR. A reduction in LF microfilaria prevalence from 2.5% (n = 13/522) in 2006 to 0.0% (n = 602) in 2014 was observed. LF TAS1 conducted in 2015 among 1,532 children 6–7 years, all were negative for antigens of W. bancrofti. Conclusion The results concluded that interruption of onchocerciasis and LF has been achieved. PMID:29253862

Human ocular onchocerciasis caused by Onchocerca lupi (Spirurida, Onchocercidae) in Iran.

PubMed

Mowlavi, G; Farzbod, F; Kheirkhah, A; Mobedi, I; Bowman, D D; Naddaf, S R

2014-06-01

Cases of canine onchocerciasis caused by Onchocerca lupi are increasingly reported from Europe and the western United States of America. The zoonotic role of this parasite had already been suspected in Europe as the clinical signs and histopathology seen in two ocular cases from Albania and the Crimean region were very similar to those of canine ocular onchocerciasis. In the most recent reports of human onchocerciasis, O. lupi has been morphologically and molecularly identified as the causative agent of ocular infestation in two patients from Turkey, and one patient from Tunisia. Here, we report an additional case of nodular lesions involving two, and possibly more, immature worms in a patient from Iran. The parasite was found to belong to the genus Onchocerca based on morphological features and the species was confirmed as O. lupi from a partial sequence analysis of 12S ribosomal DNA.

DISTRIBUTION AND UTILISATION OF IVERMECTIN (MECTIZAN): A CHEMOTHERAPEUTIC APPROACH TO THE CONTROL OF ONCHOCERCIASIS IN OLD OHAOZARA LGA, EBONYI STATE, EASTERN NIGERIA.

PubMed

Okpara, Elom Michael; Mnaemeka, Alo Moses; Iyioku, Ugah Uchenna; Udoh, Usanga Victor

2015-12-01

Onchocerciasis (river blindness) is a devastating, debilitating Stigmatising and incapacitating parasitic disease that is endemic in tropical and subtropical regions of the world, including Nigeria. Mass distribution of ivermectin (Mectizan) to the endemic parts of the world was initiated by the Onchocerciasis Control Programmes (OCPs). Absolute compliance to the regimen for up to 15 years has been reported to be effective in the control of the disease. The study was carried out in Ohaozara LGA, Onicha LGA and Ivo LGA. The three (3) LGAs made up the defunct Old Ohaozara LGA. A structured questionnaire was used to generate information on knowledge of Onchocerciasis and on the use of ivermectin by the inhabitants of the communities of the study areas. The distribution coverage of ivermectin in the study areas dating from 2010 to 2014 was ascertained with drug distribution charts obtained from Ebonyi State Health Management Board (ESHMB), Abakaliki (the point source of distribution in the state), and from the health centres in communities of old Ohaozara LGA (the service delivery points (SDPs) to inhabitants of the communities. Data was analysed using descriptive statistics. Utilization of the regimen was ascertained by determining the actual number of tablets of mectizan that was administered to the patients at the various health cenrtes (service delivery points (SDPs) in the communities. The percentage utilization of the regimen was determined by dividing the number of mectizan tablets administered to the patients at SDPs with the number of mectizan tablets supplied from state point source of distribution and multiplying by 100. A total of 347, 299 out of 1, 919135 tablets of mectizan supplied to the study areas from 2010 to 2014 were actually utilized, forming an overall percentage utilization of 18.10%. There was adequate supply but very poor utilization of the regimen. The poor utilization resulted from factors including locating of health centres very far from homes of some of the rural villagers, non-yearly compliance with regimen administration, poor health sensitization and education and lack of incentives orpoor incentives to the village-based health workers (VBHWs). Intensification of efforts to cover the lapses in the utilization of the regimen is advocated for a more effective control of the disease.

Successful control of onchocerciasis vectors in San Vicente Pacaya, Guatemala, 1984-1989.

PubMed

Ochoa, J O; Castro, J C; Barrios, V M; Juarez, E L; Tada, I

1997-07-01

Between 1984 and 1989, the onchocerciasis-vector control zone on the pilot area of San Vicente Pacaya, Guatemala, which had been subject to experimental control since 1979, was extended from 91.3 to 148.6 km2. Temephos was used as a larvicide against Simulium ochraceum s.l. the target species. As a new strategy, only breeding sites with water discharges of 0.1-10 litres/s were treated, every 2 weeks. This approach provided a substantial reduction in effort, number of treated sites, time and cost. To assess the effect of the temephos, nine sites were selected in which standardized collections of adult Simulium were made twice a month, by human bait. There was an obvious difference between the pre- and post-control mean densities of flies at each site. In the northern area, which includes the Lavaderos, Barretal, Colina and Rodeo sites, the biting density in 1979, before treatment, varied between 10 and 64 flies/man-hour (FMH). Four years later, this had been reduced to 0.1-3.2 FMH, and by the end of the present study, in 1989, the mean density was zero FMH. In the southern area, which lies south-east of Lavaderos (and includes Guachipilin, Ingerto, Pena Blanca and Sierra Morena), the density during the pre-control phase was 24 FMH at one of the two sites investigated at the time and 39.3 FMH at the other. It fell to 0.1-0.5 FMH after 5 years of control and to zero (three sites) or close to zero (< or = 0.5 FMH; one site) for the last 4 years of the present study. To assess the effect of vector control on onchocerciasis prevalence and incidence, 1280 residents from six endemic communities, out of 12,000 permanent inhabitants, were examined. In Santa Cruz, Patrocinio and Los Rios, the prevalence of skin microfilariae in the subjects from each community fell from 8.1%-37.8% during the pretreatment, base-line period to 0.0%-31.5% when the study foci were totally integrated into the vector-control operation following treatment. Incidence among children (aged < or = 9 years) varied from 0%-25% for the period 1982-1984 but, thereafter, not a single case appeared in four of the six study communities (Santa Cruz, Patrocinio, Los Rios and Berlin). Incidence in Guachipilin did not decline appreciably, probably because of human migration into the area from other onchocerciasis foci. The prevalence of nodules followed a similar trend to those of the prevalence and incidence of skin microfilariae, falling from 9.1%-45.0% pre-control to 1.8%-14.3% 10 years later.

Ocular Onchocerciasis in the Yanomami Communities from Brazilian Amazon: Effects on Intraocular Pressure

PubMed Central

Herzog-Neto, Guilherme; Jaegger, Karen; do Nascimento, Erika S.; Marchon-Silva, Verônica; Banic, Dalma M.; Maia-Herzog, Marilza

2014-01-01

To determine the influence of onchocercal eye disease on the intraocular pressure of the Yanomami Tribe Aratha-ú of Roraima State, Brazil, considered endemic for onchocerciasis, a total of 86 patients were submitted to an ophthalmologic exam that included external examination, slit lamp examination, intraocular pressure measurement, and a fundus ophthalmoscope examination. A high prevalence of onchocerciasis-related eye lesions was encountered in 68.6% of the patients. Punctate keratitis and microfilariae in the anterior chamber were found in ∼28%. The mean of intraocular eye pressure found was 10.47 mm of Hg. PMID:24297812

Ocular onchocerciasis in the Yanomami communities from Brazilian Amazon: effects on intraocular pressure.

PubMed

Herzog-Neto, Guilherme; Jaegger, Karen; Nascimento, Erika S do; Marchon-Silva, Verônica; Banic, Dalma M; Maia-Herzog, Marilza

2014-01-01

To determine the influence of onchocercal eye disease on the intraocular pressure of the Yanomami Tribe Aratha-ú of Roraima State, Brazil, considered endemic for onchocerciasis, a total of 86 patients were submitted to an ophthalmologic exam that included external examination, slit lamp examination, intraocular pressure measurement, and a fundus ophthalmoscope examination. A high prevalence of onchocerciasis-related eye lesions was encountered in 68.6% of the patients. Punctate keratitis and microfilariae in the anterior chamber were found in ∼28%. The mean of intraocular eye pressure found was 10.47 mm of Hg.

Community Attitudes toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases after the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia

PubMed Central

Bogus, Joshua; Gankpala, Lincoln; Fischer, Kerstin; Krentel, Alison; Weil, Gary J.; Fischer, Peter U.; Kollie, Karsor; Bolay, Fatorma K.

2016-01-01

The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. PMID:26666700

Risk factors for epilepsy in Bas-Uélé Province, Democratic Republic of the Congo: a case-control study.

PubMed

Colebunders, Robert; Mandro, Michel; Mokili, John L; Mucinya, Gisele; Mambandu, Germain; Pfarr, Kenneth; Reiter-Owona, Ingrid; Hoerauf, Achim; Tepage, Floribert; Levick, Bethanie; Begon, Michael; Laudisoit, Anne

2016-08-01

The reason for the high prevalence of epilepsy in onchocerciasis endemic areas remains unknown. The aim of this study was to detect risk factors associated with epilepsy in a region endemic for onchocerciasis. In June 2014, a case-control study was performed in Titule, Bas-Uélé Province in the Democratic Republic of the Congo. Individuals with unprovoked convulsive epilepsy of unknown aetiology were enrolled as cases (n=59). Healthy members of families without cases of epilepsy in the same village were recruited as controls (n=61). A multivariate binomial logistic regression analysis was performed to identify potential risk factors associated with epilepsy. To evaluate the potential protective effect of ivermectin treatment on the development of epilepsy, a nested age-matched case-control study was performed including only those who were eligible for ivermectin treatment in the year before they developed epilepsy. Suspected onchocerciasis skin lesions were more often present in cases than in controls: 12/41 (29%) vs. 1/56 (2%), respectively (odds ratio (OR) 20.26, 95% confidence interval (CI) 2.42-170; p<0.01). Ivermectin had been taken 7 months earlier in 29/59 (49%) cases and 29/61 (48%) controls. Onchocerca volvulus (OV) DNA was detected by PCR in skin snips in 26/34 cases (76%) and 10/14 controls (71%) (p=0.7), and there was presence of OV IgG4 antibodies in 35/48 (73%) cases and 15/18 (83%) controls (p=0.5). OV DNA was not detected in the cerebrospinal fluid of cases (controls not tested). Both cases and controls reported frequent bites by blackflies (Diptera, Simuliidae). Bathing daily as opposed to less often (OR 16.7, 95% CI 2.2-125.8; p<0.01), bathing between 11 a.m. and 4 p.m. (OR 12.7, 95% CI 1.6-103.7; p=0.02), and washing clothes between 11 a.m. and 4 p.m. (OR 10.9, 95% CI 1.5-77.3; p=0.02) were all independently associated with epilepsy. Blood screening by specific PCR tests for Toxoplasma and Wuchereria bancrofti was negative in all cases and controls. A Loa loa infestation was found in only one case and one control by PCR and Giemsa smear. Antibodies to Taenia solium, Toxocara, and Trypanosoma sp were not detected in any of the participants. In an age-matched case-control analysis, 16/18 (89%) cases had not taken ivermectin the year before they developed epilepsy, compared to 7/18 (39%) controls that same year (p=0.002). These data suggest that frequent activities at rivers known to be blackfly breeding sites and a historical lack of ivermectin treatment were risk factors for epilepsy in this onchocerciasis endemic area. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Mapping the distribution of Loa loa in Cameroon in support of the African Programme for Onchocerciasis Control

PubMed Central

Thomson, Madeleine C; Obsomer, Valérie; Kamgno, Joseph; Gardon, Jacques; Wanji, Samuel; Takougang, Innocent; Enyong, Peter; Remme, Jan H; Molyneux, David H; Boussinesq, Michel

2004-01-01

Background Loa loa has recently emerged as a filarial worm of significant public health importance as a consequence of its impact on the African Programme for Onchocerciasis Control (APOC). Severe, sometimes fatal, encephalopathic reactions to ivermectin (the drug of choice for onchocerciasis control) have occurred in some individuals with high Loa loa microfilarial counts. Since high density of Loa loa microfilariae is known to be associated with high prevalence rates, a distribution map of the latter may determine areas where severe reactions might occur. The aim of the study was to identify variables which were significantly associated with the presence of a Loa microfilaraemia in the subjects examined, and to develop a spatial model predicting the prevalence of the Loa microfilaraemia. Methods Epidemiological data were collected from 14,225 individuals living in 94 villages in Cameroon, and analysed in conjunction with environmental data. A series of logistic regression models (multivariate analysis) was developed to describe variation in the prevalence of Loa loa microfilaraemia using individual level co-variates (age, sex, μl of blood taken for examination) and village level environmental co-variates (including altitude and satellite-derived vegetation indices). Results A spatial model of Loa loa prevalence was created within a geographical information system. The model was then validated using an independent data set on Loa loa distribution. When considering both data sets as a whole, and a prevalence threshold of 20%, the sensitivity and the specificity of the model were 81.7 and 69.4%, respectively. Conclusions The model developed has proven very useful in defining the areas at risk of post-ivermectin Loa-related severe adverse events. It is now routinely used by APOC when projects of community-directed treatment with ivermectin are examined. PMID:15298709

Mapping the distribution of Loa loa in Cameroon in support of the African Programme for Onchocerciasis Control.

PubMed

Thomson, Madeleine C; Obsomer, Valérie; Kamgno, Joseph; Gardon, Jacques; Wanji, Samuel; Takougang, Innocent; Enyong, Peter; Remme, Jan H; Molyneux, David H; Boussinesq, Michel

2004-08-06

BACKGROUND: Loa loa has recently emerged as a filarial worm of significant public health importance as a consequence of its impact on the African Programme for Onchocerciasis Control (APOC). Severe, sometimes fatal, encephalopathic reactions to ivermectin (the drug of choice for onchocerciasis control) have occurred in some individuals with high Loa loa microfilarial counts. Since high density of Loa loa microfilariae is known to be associated with high prevalence rates, a distribution map of the latter may determine areas where severe reactions might occur. The aim of the study was to identify variables which were significantly associated with the presence of a Loa microfilaraemia in the subjects examined, and to develop a spatial model predicting the prevalence of the Loa microfilaraemia. METHODS: Epidemiological data were collected from 14,225 individuals living in 94 villages in Cameroon, and analysed in conjunction with environmental data. A series of logistic regression models (multivariate analysis) was developed to describe variation in the prevalence of Loa loa microfilaraemia using individual level co-variates (age, sex, microl of blood taken for examination) and village level environmental co-variates (including altitude and satellite-derived vegetation indices). RESULTS: A spatial model of Loa loa prevalence was created within a geographical information system. The model was then validated using an independent data set on Loa loa distribution. When considering both data sets as a whole, and a prevalence threshold of 20%, the sensitivity and the specificity of the model were 81.7 and 69.4%, respectively. CONCLUSIONS: The model developed has proven very useful in defining the areas at risk of post-ivermectin Loa-related severe adverse events. It is now routinely used by APOC when projects of community-directed treatment with ivermectin are examined.

Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.

PubMed

Gardon, J; Gardon-Wendel, N; Demanga-Ngangue; Kamgno, J; Chippaux, J P; Boussinesq, M

1997-07-05

In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic. Ivermectin (at 150 micrograms/kg) was given to 17877 people living in the Lékié area of Cameroon. 50 microL samples of capillary blood were taken during the daytime before treatment from all adults (aged > or = 15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model. 20 patients (0-11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2-3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio > 1000) for loads above 50000 microfilariae/mL. Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.

Lack of resistance after re-exposure of cattle cured of Onchocerca ochengi infection with oxytetracycline.

PubMed

Nfon, Charles K; Makepeace, Benjamin L; Njongmeta, Leo M; Tanya, Vincent N; Trees, Alexander J

2007-01-01

Although vector control and ivermectin chemotherapy have led to a dramatic reduction in the incidence of river blindness (onchocerciasis), there is a consensus that additional control tools are required to sustain and extend this success. The recognition of endosymbiotic bacteria (Wolbachia) in filariae and their targeting by antibiotics constitutes the most significant and practicable opportunity for a macrofilaricidal therapy in the short-to-medium-term. Using Onchocerca ochengi in cattle, an analog of human onchocerciasis, we have previously shown that oxytetracycline is macrofilaricidal, and protective immunity exists naturally in a subset of animals termed putatively immune. Here, we report that although 24 weeks of weekly oxytetracycline treatment eliminated adult worms, cured animals remained susceptible to re-infection by natural challenge when compared with putatively immune cattle. However, their susceptibility was not significantly different from that of concurrently exposed, heavily infected animals. Thus, cattle cured by oxytetracycline are neither hypo-susceptible nor hyper-susceptible.

Investing in Justice: Ethics, Evidence, and the Eradication Investment Cases for Lymphatic Filariasis and Onchocerciasis

PubMed Central

Merritt, Maria W.; Tediosi, Fabrizio

2015-01-01

It has been suggested that initiatives to eradicate specific communicable diseases need to be informed by eradication investment cases to assess the feasibility, costs, and consequences of eradication compared with elimination or control. A methodological challenge of eradication investment cases is how to account for the ethical importance of the benefits, burdens, and distributions thereof that are salient in people’s experiences of the diseases and related interventions but are not assessed in traditional approaches to health and economic evaluation. We have offered a method of ethical analysis grounded in theories of social justice. We have described the method and its philosophical rationale and illustrated its use in application to eradication investment cases for lymphatic filariasis and onchocerciasis, 2 neglected tropical diseases that are candidates for eradication. PMID:25713967

Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis.

PubMed Central

Taylor, H R; Greene, B M

1981-01-01

Twenty men with moderate infection of Onchocerca volvulus were studied in a double-masked, controlled clinical trial to compare the safety and efficacy of oral diethylcarbamazine (DEC) with topical DEC lotion. Visual acuity and colour vision did not alter during the 6 months of observation, although 2 patients receiving DEC lotion and 3 patients receiving oral DEC developed either visual field constriction or optic atrophy. Fluffy corneal opacities were common in both groups. Intraocular microfilariae also appeared in both groups but to a greater extent in those receiving DEC lotion. New chorioretinal changes developed in 4 men receiving lotion and in only 1 receiving tablets. It is concluded that DEC lotion offers no advantage over tablets in the treatment of ocular onchocerciasis and in fact may be associated with more ocular complications than the conventional oral treatment. Images PMID:7020746

Impact of 3 years ivermectin treatment on onchocerciasis in Yanomami communities in the Brazilian Amazon.

PubMed

Banic, Dalma M; Calvão-Brito, Regina H S; Marchon-Silva, Verônica; Schuertez, Joana C; de Lima Pinheiro, Luís Renerys; da Costa Alves, Marilene; Têva, Antônio; Maia-Herzog, Marilza

2009-11-01

In the current study, it was assessed, for the first time, the effect of ivermectin treatment administered twice a year on the prevalence and morbidity of onchocerciasis in the hyperendemic Yanomami communities of the Roraima State (Brazil). Physical and parasitological examinations were carried out every 6 months until six drug rounds of treatment were completed. The coverage during the six rounds of ivermectin treatment ranged from 89% to 92% of the eligible Yanomami population. Overall, comparison of results at pre-treatment with results after six rounds of treatment, the prevalence of infection had declined from 87% to 42% (P<0.0001, CI 95%=0.05-0.22); the community microfilarial load (CMFL) fell from 1.17 to 0.53Mf/mg of skin; and the crude intensity of infection (MFL-Total) decreased from 18.95 to 1.96Mf/mg of skin during the same period (P<0.0001, for both microfilarial loads). Although no significant difference was observed between microfilarial densities in skin snips from iliac crest and scapula after the 6th round of ivermectin treatment it was observed that the prevalence of positive skin snips was significantly higher when skin snips were taken from iliac crest (42%) than from scapula (8%) (P=0.001, CI 95%=3.41-22.67). After six rounds of ivermectin treatments, no significant differences were observed in the prevalences of palpable nodules and of onchodermatitis in relation to pre-treatment prevalences, from 45% to 41% and from 17% to 20% (P>0.05, for both). These findings suggest that mass population treatment should continue without interruption and achieve higher levels of drug coverage in order to alleviate disease manifestations and interrupt infection transmission to hasten the elimination of onchocerciasis in Yanomami communities. In addition, the sensitivity of iliac crest snips for parasitological assessment in epidemiological surveillance of Yanomami communities may increase the acceptance of the population in biopsy sampling and seems to be a good choice for assessing the success of control programs.

An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District, Uganda

PubMed Central

Foltz, Jennifer L.; Makumbi, Issa; Sejvar, James J.; Malimbo, Mugagga; Ndyomugyenyi, Richard; Atai-Omoruto, Anne Deborah; Alexander, Lorraine N.; Abang, Betty; Melstrom, Paul; Kakooza, Angelina M.; Olara, Dennis; Downing, Robert G.; Nutman, Thomas B.; Dowell, Scott F.; Lwamafa, D. K. W.

2013-01-01

Introduction Nodding Syndrome (NS), an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda. Methods In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations. Results Surveillance identified 224 cases; most (95%) were 5–15-years-old (range = 2–27). Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0·6–46). The case-control investigation (n = 49 case/village control pairs) showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR1) = 14·4 (2·7, 78·3)], exposure to munitions [AOR1 = 13·9 (1·4, 135·3)], and consumption of crushed roots [AOR1 = 5·4 (1·3, 22·1)] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84%) and controls (75%). Conclusion NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies. PMID:23823012

Co-endemicity of loiasis and onchocerciasis in rain forest communities in southwestern Nigeria.

PubMed

Ojurongbe, Olusola; Akindele, Akeem Abiodun; Adeleke, Monsuru Adebayo; Oyedeji, Matthew Oyebode; Adedokun, Samuel Adeyinka; Ojo, Josephine Folashade; Akinleye, Callistus Adewale; Bolaji, Oloyede Samuel; Adefioye, Olusegun Adelowo; Adeyeba, Oluwaseyi Adegboyega

2015-03-01

Loiasis is currently receiving attention as a disease of public health importance because of the possibility of increased risk of developing neurologic serious adverse event following mass ivermectin treatment against onchocerciasis in individual co-infected with Onchocerca volvulus and Loa loa. Rapid assessment procedure for loiasis (RAPLOA) was conducted in 12 communities covering the 3 senatorial districts of Osun State, Nigeria. A total of 960 people were interviewed for history of eye worm using the WHO guidelines for rapid assessment. The survey confirmed the presence of loiasis in all the 12 communities with 4 in Osun East/Ife south senatorial district being at high risk with a prevalence of over 40%. Based on the RAPLOA results, communities within Osun East/Ife south senatorial district were selected for microfilaraemic assessment of L. loa and O. volvulus. A total of 1115 and 1091 individuals were screened for L. loa and O. volvulus microfilaria worms respectively. 160 (14.3%) had L. loa microfilaria detected in their blood with 8 (5.0%) individuals having L. loa loads above 8000 mf/ml. 166 (15.2%) subjects had O. volvulus microfilaria (range 4-504 mf/ml) detected in their skin snip. 30 (2.69%) subjects were co-infected with both L. loa and O. volvulus. There was a significant variation in the prevalence (2.1% to 33.3%) of onchocerciasis in the communities studied (p = 0.001). Five (41.7%) of the studied communities had a prevalence that is equal to or greater than 20%. Low prevalence of onchocerciasis and loiasis co-infection in this study suggests that loiasis may not pose a serious epidemiological threat to the continuous distribution and sustainability of ivermectin for the treatment of onchocerciasis. Evaluation of the interruption of onchocerciasis transmissions in this region using all the indicators set forth by WHO is therefore suggested.

Interruption of infection transmission in the onchocerciasis focus of Ecuador leading to the cessation of ivermectin distribution.

PubMed

Lovato, Raquel; Guevara, Angel; Guderian, Ronald; Proaño, Roberto; Unnasch, Thomas; Criollo, Hipatia; Hassan, Hassan K; Mackenzie, Charles D

2014-05-01

A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. Thirty-five rounds of ivermectin treatment occurred between 1991-2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39-101) and 72.7 (CI 42-116) in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1-15 years (between 82 and 98% of children present in the surveyed villages) tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption.

Interruption of Infection Transmission in the Onchocerciasis Focus of Ecuador Leading to the Cessation of Ivermectin Distribution

PubMed Central

Lovato, Raquel; Guevara, Angel; Guderian, Ronald; Proaño, Roberto; Unnasch, Thomas; Criollo, Hipatia; Hassan, Hassan K.; Mackenzie, Charles D.

2014-01-01

Introduction: A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. Methodology and Principle Findings: Thirty-five rounds of ivermectin treatment occurred between 1991–2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39–101) and 72.7 (CI 42–116) in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1–15 years (between 82 and 98% of children present in the surveyed villages) tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. Significance: This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption. PMID:24853587

A novel rapid test for detecting antibody responses to Loa loa infections.

PubMed

Pedram, Bijan; Pasquetto, Valérie; Drame, Papa M; Ji, Yongchang; Gonzalez-Moa, Maria J; Baldwin, Richard K; Nutman, Thomas B; Biamonte, Marco A

2017-07-01

Ivermectin-based mass drug administration (MDA) programs have achieved remarkable success towards the elimination of onchocerciasis and lymphatic filariasis. However, their full implementation has been hindered in Central Africa by the occurrence of ivermectin-related severe adverse events (SAEs) in a subset of individuals with high circulating levels of Loa loa microfilariae. Extending MDA to areas with coincident L. loa infection is problematic, and inexpensive point-of-care tests for L. loa are acutely needed. Herein, we present a lateral flow assay (LFA) to identify subjects with a serological response to Ll-SXP-1, a specific and validated marker of L. loa. The test was evaluated on serum samples from patients infected with L. loa (n = 109) and other helminths (n = 204), as well as on uninfected controls (n = 77). When read with the naked eye, the test was 94% sensitive for L. loa infection and was 100% specific when sera from healthy endemic and non-endemic controls or from those with S. stercoralis infections were used as the comparators. When sera of patients with O. volvulus, W. bancrofti, or M. perstans were used as the comparators, the specificity of the LFA was 82%, 87%, and 88%, respectively. A companion smartphone reader allowed measurement of the test line intensities and establishment of cutoff values. With a cutoff of 600 Units, the assay sensitivity decreased to 71%, but the specificity increased to 96% for O. volvulus, 100% for W. bancrofti, and 100% for M. perstans-infected individuals. The LFA may find applications in refining the current maps of L. loa prevalence, which are needed to eliminate onchocerciasis and lymphatic filariasis from the African continent.

Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis

PubMed Central

Bulman, Christina A.; Bidlow, Chelsea M.; Lustigman, Sara; Cho-Ngwa, Fidelis; Williams, David; Rascón, Jr, Alberto A.; Tricoche, Nancy; Samje, Moses; Bell, Aaron; Suzuki, Brian; Lim, K. C.; Supakorndej, Nonglak; Supakorndej, Prasit; Wolfe, Alan R.; Knudsen, Giselle M.; Chen, Steven; Wilson, Chris; Ang, Kean-Hooi; Arkin, Michelle; Gut, Jiri; Franklin, Chris; Marcellino, Chris; McKerrow, James H.; Debnath, Anjan; Sakanari, Judy A.

2015-01-01

Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s) of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC50 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC50 against the microfilariae of L. loa compared with the IC50 for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode. PMID:25700363

Status of forest onchocerciasis in the Lower Cross River basin, Nigeria: entomologic profile after five years of ivermectin intervention.

PubMed

Opara, Kenneth N; Fagbemi, Olakunle B; Ekwe, Asuquo; Okenu, Daniel M N

2005-08-01

In the Lower Cross River basin in Nigeria, no pre-control entomologic profile of Onchocerca volvulus infection in the local Simulium damnosum population was available prior to the initiation of an ivermectin control program in 1995. A longitudinal entomologic study was therefore carried out over a 12-month period (January-December 2001) at the Agbokim waterfalls and Afi River, which are breeding sites of S. damnosum in the river basin. A total of 9,287 adult S. damnosum were caught on human bait; 9,048 (97.43%) were dissected, of which 313 (3.46%) were infected. Annual biting rates (ABRs) of 42,419 and 28,346 bites per persons per year were recorded at the Agbokim Waterfalls and Afi River, respectively. The annual transmission potential (ATP) was 419 infective larvae per person per year at the Agbokim Waterfalls and 427 at the Afi River. Monthly biting rate and monthly transmission potential varied significantly (P < 0.05) at the two sites. Transmission was highly seasonal from April to September, corresponding to the peak biting period of the vector. The high ATP and ABR values are a measure of the mesoendemicity of onchocerciasis in the river basin. There was a significant F(0).05 (1, 10) (P < 0.05) variation in the relative fly abundance from both sites. It was observed that human activities such as farming, fishing, timber cutting, and hunting are done in the early morning and late afternoon, which corresponds to the peak diurnal biting period of the vector. Changes in these practices and attitudes may markedly affect the disease intensity and transmission.

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

PubMed Central

Tchakouté, Virginia L.; Graham, Simon P.; Jensen, Siv Aina; Makepeace, Benjamin L.; Nfon, Charles K.; Njongmeta, Leo M.; Lustigman, Sara; Enyong, Peter A.; Tanya, Vincent N.; Bianco, Albert E.; Trees, Alexander J.

2006-01-01

Onchocerciasis (river blindness) is a major parasitic disease of humans in sub-Saharan Africa caused by the microfilarial stage of the nematode Onchocerca volvulus. Using Onchocerca ochengi, a closely related species which infects cattle and is transmitted by the same black fly vector (Simulium damnosum sensu lato) as O. volvulus, we have conducted longitudinal studies after either natural field exposure or experimental infection to determine whether, and under what circumstances, protective immunity exists in onchocerciasis. On the basis of the adult worm burdens (nodules) observed, we determined that cattle reared in endemic areas without detectable parasites (putatively immune) were significantly less susceptible to heavy field challenge than age-matched, naïve controls (P = 0.002), whereas patently infected cattle, cured of infection by adulticide treatment with melarsomine, were fully susceptible. Cattle immunized with irradiated third-stage larvae were significantly protected against experimental challenge (100% reduction in median nodule load, P = 0.003), and vaccination also conferred resistance to severe and prolonged field challenge (64% reduction in median nodule load, P = 0.053; and a significant reduction in microfilarial positivity rates and density, P < 0.05). These results constitute evidence of protective immunity in a naturally evolved host–Onchocerca sp. relationship and provide proof-of-principle for immunoprophylaxis under experimental and field conditions. PMID:16585501

Pathogenesis of Onchocercal Keratitis (River Blindness)

PubMed Central

Hall, Laurie R.; Pearlman, Eric

1999-01-01

Onchocerciasis is a major cause of blindness. Although the World Health Organization has been successful in reducing onchocerciasis as a public health problem in parts of West Africa, there remain an estimated 17 million people infected with Onchocerca volvulus, the parasite that causes this disease. Ocular pathology can be manifested in any part of the eye, although disease manifestations are frequently characterized as either posterior or anterior eye disease. This review focuses on onchocerca-mediated keratitis that results from an inflammatory response in the anterior portion of the eye and summarizes what is currently known about human disease. This review also describes studies with experimental models that have been established to determine the immunological mechanisms underlying interstitial keratitis. The pathogenesis of keratitis is thought to be due to the host inflammatory response to degenerating parasites in the eye; therefore, the primary clinical symptoms of onchocercal keratitis (corneal opacification and neovascularization) are induced after injection of soluble O. volvulus antigens into the corneal stroma. Experimental approaches have demonstrated an essential role for sensitized T helper cells and shown that cytokines can regulate the severity of keratitis by controlling recruitment of inflammatory cells into the cornea. Chemokines are also important in inflammatory cell recruitment to the cornea, and their role in onchocerciasis is being examined. Further understanding of the molecular basis of the development of onchocercal keratitis may lead to novel approaches to immunologically based intervention. PMID:10398675

Diurnal biting periodicity of parous Simulium (Diptera: Simuliidae) vectors in the onchocerciasis Amazonian focus.

PubMed

Grillet, M-E; Villamizar, N J; Cortez, J; Frontado, H L; Escalona, M; Vivas-Martínez, S; Basáñez, M-G

2005-05-01

We describe the hourly patterns of parous biting activity of the three main simuliid vectors of human onchocerciasis in the Amazonian focus straddling between Venezuela and Brazil, namely, Simulium guianense s.l. Wise; S. incrustatum Lutz, and S. oyapockense s.l. Floch and Abonnenc. Time series of the hourly numbers of host-seeking parous flies caught in five Yanomami villages during dry, rainy, and their transition periods from 1995 to 2001 were investigated using harmonic analysis (assuming an underlying circadian rhythm) and periodic correlation (based on Spearman's r). Parous S guianense s.l. showed a bimodal activity pattern, with a minor peak in mid-morning and a major peak at 16:00 h. S. incrustatum exhibited mainly unimodal activity during either early morning or midday according to locality. S. oyapockense s.l. bit humans throughout the day mainly between 10:00 and 16:00 h but also showed bimodal periodicity in some localities. Superimposed on the endogenous, species-specific daily cycles, parous activity showed variation according to locality, season, air temperature and relative humidity, with biting being promoted by warmer and drier hours during wet seasons/periods and reduced during hotter times in dry seasons or transitions. The results are discussed in terms of their implications for blackfly biology and ecology as well as onchocerciasis epidemiology and control.

Community Attitudes Toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases After the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia.

PubMed

Bogus, Joshua; Gankpala, Lincoln; Fischer, Kerstin; Krentel, Alison; Weil, Gary J; Fischer, Peter U; Kollie, Karsor; Bolay, Fatorma K

2016-03-01

The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. © The American Society of Tropical Medicine and Hygiene.

The elimination of the onchocerciasis vector from the island of Bioko as a result of larviciding by the WHO African Programme for Onchocerciasis Control.

PubMed

Traoré, S; Wilson, M D; Sima, A; Barro, T; Diallo, A; Aké, A; Coulibaly, S; Cheke, R A; Meyer, R R F; Mas, J; McCall, P J; Post, R J; Zouré, H; Noma, M; Yaméogo, L; Sékétéli, A V; Amazigo, U V

2009-09-01

The island of Bioko is part of the Republic of Equatorial Guinea and is the only island in the World to have endemic onchocerciasis. The disease is hyperendemic and shows a forest-type epidemiology with low levels of blindness and high levels of skin disease, and the whole population of 68,000 is estimated to be at risk. Control of onchocerciasis began in 1990 using ivermectin and this yielded significant clinical benefits but transmission was not interrupted. Feasibility and preparatory studies carried out between 1995 and 2002 confirmed the probable isolation of the vector on the island, the high vectorial efficiency of the Bioko form of Simulium yahense, the seasonality of river flow, blackfly breeding and biting densities, and the distribution of the vector breeding sites. It was proposed that larviciding should be carried out from January to April, when most of the island's rivers were dry or too low to support Simulium damnosum s.l., and that most rivers would not need to be treated above 500 m altitude because they were too small to support the breeding of S. damnosum s.l. Larviciding (with temephos) would need to be carried out by helicopter (because of problems of access by land), supplemented by ground-based delivery. Insecticide susceptibility trials showed that the Bioko form was highly susceptible to temephos, and insecticide carry was tested in the rivers by assessing the length of river in which S. damnosum s.l. larvae were killed below a temephos dosing point. Regular fly catching points were established in 1999 to provide pre-control biting densities, and to act as monitoring points for control efforts. An environmental impact assessment concluded that the proposed control programme could be expected to do little damage, and a large-scale larviciding trial using ground-based applications of temephos (Abate 20EC) throughout the northern (accessible) part of the island was carried out for five weeks from 12 February 2001. Following this, a first attempt to eliminate the vectors was conducted using helicopter and ground-based applications of temephos from February to May 2003, but this was not successful because some vector populations persisted and subsequently spread throughout the island. A second attempt from January to May 2005 aimed to treat all flowing watercourses and greatly increased the number of treatment points. This led to the successful elimination of the vector. The last biting S. damnosum s.l. was caught in March 2005 and none have been found since then for more than 3 years.

O-5S quantitative real-time PCR: a new diagnostic tool for laboratory confirmation of human onchocerciasis.

PubMed

Mekonnen, Solomon A; Beissner, Marcus; Saar, Malkin; Ali, Solomon; Zeynudin, Ahmed; Tesfaye, Kassahun; Adbaru, Mulatu G; Battke, Florian; Poppert, Sven; Hoelscher, Michael; Löscher, Thomas; Bretzel, Gisela; Herbinger, Karl-Heinz

2017-10-02

Onchocerciasis is a parasitic disease caused by the filarial nematode Onchocerca volvulus. In endemic areas, the diagnosis is commonly confirmed by microscopic examination of skin snip samples, though this technique is considered to have low sensitivity. The available melting-curve based quantitative real-time PCR (qPCR) using degenerated primers targeting the O-150 repeat of O. volvulus was considered insufficient for confirming the individual diagnosis, especially in elimination studies. This study aimed to improve detection of O. volvulus DNA in clinical samples through the development of a highly sensitive qPCR assay. A novel hydrolysis probe based qPCR assay was designed targeting the specific sequence of the O. volvulus O-5S rRNA gene. A total of 200 clinically suspected onchocerciasis cases were included from Goma district in South-west Ethiopia, from October 2012 through May 2013. Skin snip samples were collected and subjected to microscopy, O-150 qPCR, and the novel O-5S qPCR. Among the 200 individuals, 133 patients tested positive (positivity rate of 66.5%) and 67 negative by O-5S qPCR, 74 tested positive by microscopy (37.0%) and 78 tested positive by O-150 qPCR (39.0%). Among the 133 O-5S qPCR positive individuals, microscopy and O-150 qPCR detected 55.6 and 59.4% patients, respectively, implying a higher sensitivity of O-5S qPCR than microscopy and O-150 qPCR. None of the 67 individuals who tested negative by O-5S qPCR tested positive by microscopy or O-150 qPCR, implying 100% specificity of the newly designed O-5S qPCR assay. The novel O-5S qPCR assay is more sensitive than both microscopic examination and the existing O-150 qPCR for the detection of O. volvulus from skin snip samples. The newly designed assay is an important step towards appropriate individual diagnosis and control of onchocerciasis.

Doxycycline Leads to Sterility and Enhanced Killing of Female Onchocerca volvulus Worms in an Area With Persistent Microfilaridermia After Repeated Ivermectin Treatment: A Randomized, Placebo-Controlled, Double-Blind Trial

PubMed Central

Debrah, Alexander Yaw; Specht, Sabine; Klarmann-Schulz, Ute; Batsa, Linda; Mand, Sabine; Marfo-Debrekyei, Yeboah; Fimmers, Rolf; Dubben, Bettina; Kwarteng, Alexander; Osei-Atweneboana, Mike; Boakye, Daniel; Ricchiuto, Arcangelo; Büttner, Marcelle; Adjei, Ohene; Mackenzie, Charles D.; Hoerauf, Achim

2015-01-01

Background. Ivermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response. Methods. One hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment. Results. At 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline. Conclusions. Targeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM. Clinical Trials Registration. ISRCTN 66649839. PMID:25948064

Model-Based Geostatistical Mapping of the Prevalence of Onchocerca volvulus in West Africa

PubMed Central

O’Hanlon, Simon J.; Slater, Hannah C.; Cheke, Robert A.; Boatin, Boakye A.; Coffeng, Luc E.; Pion, Sébastien D. S.; Boussinesq, Michel; Zouré, Honorat G. M.; Stolk, Wilma A.; Basáñez, María-Gloria

2016-01-01

Background The initial endemicity (pre-control prevalence) of onchocerciasis has been shown to be an important determinant of the feasibility of elimination by mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in West Africa (OCP) before commencement of antivectorial and antiparasitic interventions. Methods and Findings Pre-control microfilarial prevalence data from 737 villages across the 11 constituent countries in the OCP epidemiological database were used as ground-truth data. These 737 data points, plus a set of statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in West Africa prior to the commencement of the OCP. Uncertainty in model predictions was measured using a suite of validation statistics, performed on bootstrap samples of held-out validation data. The mean Pearson’s correlation between observed and estimated prevalence at validation locations was 0.693; the mean prediction error (average difference between observed and estimated values) was 0.77%, and the mean absolute prediction error (average magnitude of difference between observed and estimated values) was 12.2%. Within OCP boundaries, 17.8 million people were deemed to have been at risk, 7.55 million to have been infected, and mean microfilarial prevalence to have been 45% (range: 2–90%) in 1975. Conclusions and Significance This is the first map of initial onchocerciasis prevalence in West Africa using B-MBG. Important environmental predictors of infection prevalence were identified and used in a model out-performing those without spatial random effects or environmental covariates. Results may be compared with recent epidemiological mapping efforts to find areas of persisting transmission. These methods may be extended to areas where data are sparse, and may be used to help inform the feasibility of elimination with current and novel tools. PMID:26771545

Impact of Eighteen-Year Varied Compliance to Onchocerciasis Treatment with Ivermectin in Sentinel Savannah Agrarian Communities in Kaduna State of Nigeria.

PubMed

Osue, Hudu O; Inabo, Helen I; Yakubu, Sabo E; Audu, Patrick A; Galadima, Musa; Odama, Lillian E; Musa, Danjuma; Ado, Saleh A; Mamman, Mohammed

2013-01-01

Baseline and impact assessment data were generated in 1994 (n = 532) and 2011 (n = 593) from 6 sentinel villages with generalized onchocerciasis. Only volunteers and a cohort (n = 445, 75%) were screened at both visits. Each village had received 11 (64.7%) annual treatments and 92.6%, range 88.7-100%, treatment compliance. Overall mean number of treatment was 2.9 ± 1.6 with a range 2.0 ± 1.2-3.3 ± 0.6. Significant decreases in skin microfilaria prevalence from 201 (38%) to 0 (0%), palpable nodule from 77 (15%) to 4 (0.7%), dermal changes from 51 (9.6%) to 2 (0.04%), optic nerve disease from 24 (4.5%) to 4 (2.0%), and onchocercal inducible ocular lesions from 31 (5.8%) to 12 (2.0%) were recorded, P < 0.05, (t-test of unpaired data). Cases of glaucoma, 8 (1.4%), and blindness, 6 (1.05%), remained unchanged. Visual acuity ≥6/24 in one or both eyes, 198 (33.45%); cataract, 169 (28.5%); pterygium 157 (26.5%); and acute senilis, 165 (27.9%), were significantly increased and positively correlated with increase in age (R (2) = 0.898 - 0.949). Dissected parous Simulium damnosum caught (n = 222) were without infective third stage larva. Active onchocerciasis transmission seems halted despite varied compliance to long-term ivermectin treatment. We recommend continued surveillance and targeted treatment of controlled and hypoendemic areas.

Dermatological manifestations in onchocerciasis: A retrospective study of 400 imported cases.

PubMed

Puente, Sabino; Ramirez-Olivencia, German; Lago, Mar; Subirats, Mercedes; Perez-Blazquez, Eugenio; Bru, Fernando; Garate, Teresa; Vicente, Belén; Belhassen-Garcia, Moncef; Muro, Antonio

2017-12-20

Onchocerciasis is caused by Onchocerca volvulus and mainly leads to pruritus and skin and visual disorders, including blindness. Seventeen million people are infected in 38 countries; 31 of these are in sub-Saharan Africa, six in Latin America and one on the Arabian Peninsula. More than 99% of cases occur in sub-Saharan Africa where 120 million people are at risk of infection. Eye disorders have been well-documented; however, skin disorders have not been described accurately. The objective of our study was to describe the epidemiology, main skin manifestations and treatment of imported onchocerciasis. A retrospective study was thus conducted by analysing the main demographic, clinical and treatment data regarding a cohort of 400 patients attending a reference clinical unit over a 17-year period. Most patients were female (55%) with mean age 37.5±16.7 years. All the migrants came from sub-Saharan countries. The most frequently occurring dermatological symptom was pruritus. Ivermectin had been used as first-line therapy and adverse reactions had been described in 11 patients (3.2%). The results indicate the fact that there should be a clinical suspicion of onchocerciasis regarding immigrants from endemic areas having skin lesions compatible with the disease's profile or asymptomatic patients having eosinophilia or unexplained high IgE. Moreover, skin snips from the buttocks region were very fruitful and treatment with ivermectin was seen to be safe. This is the largest case series regarding imported onchocerciasis described up to the present time. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Successful Interruption of Transmission of Onchocerca volvulus in the Escuintla-Guatemala Focus, Guatemala

PubMed Central

Gonzalez, Rodrigo J.; Cruz-Ortiz, Nancy; Rizzo, Nidia; Richards, Jane; Zea-Flores, Guillermo; Domínguez, Alfredo; Sauerbrey, Mauricio; Catú, Eduardo; Oliva, Orlando; Richards, Frank O.; Lindblade, Kim A.

2009-01-01

Background Elimination of onchocerciasis (river blindness) through mass administration of ivermectin in the six countries in Latin America where it is endemic is considered feasible due to the relatively small size and geographic isolation of endemic foci. We evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of Escuintla-Guatemala in Guatemala, based on World Health Organization criteria for the certification of elimination of onchocerciasis. Methodology/Principal Findings We conducted evaluations of ocular morbidity and past exposure to Onchocerca volvulus in the human population, while potential vectors (Simulium ochraceum) were captured and tested for O. volvulus DNA; all of the evaluations were carried out in potentially endemic communities (PEC; those with a history of actual or suspected transmission or those currently under semiannual mass treatment with ivermectin) within the focus. The prevalence of microfilariae in the anterior segment of the eye in 329 individuals (≥7 years old, resident in the PEC for at least 5 years) was 0% (one-sided 95% confidence interval [CI] 0–0.9%). The prevalence of antibodies to a recombinant O. volvulus antigen (Ov-16) in 6,432 school children (aged 6 to 12 years old) was 0% (one-sided 95% IC 0–0.05%). Out of a total of 14,099 S. ochraceum tested for O. volvulus DNA, none was positive (95% CI 0–0.01%). The seasonal transmission potential was, therefore, 0 infective stage larvae per person per season. Conclusions/Significance Based on these evaluations, transmission of onchocerciasis in the Escuintla-Guatemala focus has been successfully interrupted. Although this is the second onchocerciasis focus in Latin America to have demonstrated interruption of transmission, it is the first focus with a well-documented history of intense transmission to have eliminated O. volvulus. PMID:19333366

Onchocerciasis-related epilepsy? Prospects at a time of uncertainty.

PubMed

Marin, Benoît; Boussinesq, Michel; Druet-Cabanac, Michel; Kamgno, Joseph; Bouteille, Bernard; Preux, Pierre-Marie

2006-01-01

Epilepsy and onchocerciasis (river blindness) constitute serious public health problems in several tropical countries. There are four main mechanisms that might explain a relationship between these two diseases: (i) the presence of Onchocerca volvulus in the central nervous system; (ii) the pathogenicity of various O. volvulus strains; (iii) immunological mechanisms involving cross-reactive immunization or cytokine production during infection; and (iv) the triggering role of insomnia due to itching.

Late-onset onchocercal skin disease among Ethiopian immigrants.

PubMed

Baum, S; Greenberger, S; Pavlotsky, F; Solomon, M; Enk, C D; Schwartz, E; Barzilai, A

2014-11-01

Onchocerciasis is an infectious disease caused by the filaria Onchocerca volvulus. Very little is known regarding onchocerciasis imported from endemic to nonendemic areas. To evaluate pruritic dermatitis simulating atopic dermatitis in Ethiopian immigrants in Israel. A retrospective study of 27 Ethiopian immigrants to Israel was conducted. Demographics and clinical and laboratory data were collected. Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The average age at referral was 29 years. All of the patients emigrated from Kuwara, Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation was a combination of lichenified onchodermatitis with atrophy and depigmentation (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were treated with a single administration of oral ivermectin 200 μg mg(-1). Thirteen patients responded to the treatment. Immigrants from endemic regions to developed countries presenting with pruritic diseases, especially those with a clinical picture suggestive of atopic dermatitis, should be evaluated for possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost treatment, should be considered even in the absence of a proven disease. Physicians should have a high index of suspicion in patients with the corresponding residential history. © 2014 British Association of Dermatologists.

Loa loa vectors Chrysops spp.: perspectives on research, distribution, bionomics, and implications for elimination of lymphatic filariasis and onchocerciasis.

PubMed

Kelly-Hope, Louise; Paulo, Rossely; Thomas, Brent; Brito, Miguel; Unnasch, Thomas R; Molyneux, David

2017-04-05

Loiasis is a filarial disease caused Loa loa. The main vectors are Chrysops silacea and C. dimidiata which are confined to the tropical rainforests of Central and West Africa. Loiasis is a mild disease, but individuals with high microfilaria loads may suffer from severe adverse events if treated with ivermectin during mass drug administration campaigns for the elimination of lymphatic filariasis and onchocerciasis. This poses significant challenges for elimination programmes and alternative interventions are required in L. loa co-endemic areas. The control of Chrysops has not been considered as a viable cost-effective intervention; we reviewed the current knowledge of Chrysops vectors to assess the potential for control as well as identified areas for future research. We identified 89 primary published documents on the two main L. loa vectors C. silacea and C dimidiata. These were collated into a database summarising the publication, field and laboratory procedures, species distributions, ecology, habitats and methods of vector control. The majority of articles were from the 1950-1960s. Field studies conducted in Cameroon, Democratic Republic of Congo, Equatorial Guinea, Nigeria and Sudan highlighted that C. silacea is the most important and widespread vector. This species breeds in muddy streams or swampy areas of forests or plantations, descends from forest canopies to feed on humans during the day, is more readily adapted to human dwellings and attracted to wood fires. Main vector targeted measures proposed to impact on L. loa transmission included personal repellents, household screening, indoor residual spraying, community-based environmental management, adulticiding and larviciding. This is the first comprehensive review of the major L. loa vectors for several decades. It highlights key vector transmission characteristics that may be targeted for vector control providing insights into the potential for integrated vector management, with multiple diseases being targeted simultaneously, with shared human and financial resources and multiple impact. Integrated vector management programmes for filarial infections, especially in low transmission areas of onchocerciasis, require innovative approaches and alternative strategies if the elimination targets established by the World Health Organization are to be achieved.

Parasitological indicators of onchocerciasis relevant to ivermectin control programmes in the Amazonian focus of Southern Venezuela.

PubMed

Vivas-Martínez, S; Basáñez, M G; Botto, C; Villegas, L; García, M; Curtis, C F

2000-11-01

In the previous paper it was concluded that those aged > or = 15 years of both sexes could comprise the indicator group for rapid epidemiological assessment (REA) of onchocerciasis in the Amazonian focus. This paper explores relationships between community microfilarial (mf) prevalence, intensity, and nodule prevalence in 20 Yanomami communities, that would allow identification of REA methods in the region. The mean nodule ratio (prevalence of nodules/prevalence of mf) was 0.54 when onchocercomata in the indicator group were considered. The Spearman correlation coefficient between mf and nodule prevalence was 0.686 (P = 0.001). Palpation of nodules had 92 % specificity and 32 % sensitivity when compared to skin-snipping for the diagnosis of onchocerciasis. The predictive value positive increased from 75 % to 81 % when the indicator group was used. A microfilarial prevalence > 75 % in this group would be indicative of hyperendemic status in the village, between 30 and 75 % of mesoendemicity, and < 30 % of hypoendemicity. For the assessment of infection intensity, biopsies may be taken from the iliac crest for all endemicity levels. Five of the hyperendemic villages surveyed in this work had a community microfilarial load (CMFL) greater than 10 mf/skin snip; the remaining 5 had a CMFL between 5 and 9. These levels of infection merit high priority ivermectin treatment. In Latin America, communities at both moderate and severe risk are included in mass chemotherapy programmes (i.e. when mf prevalence is over 20 %). Roughly, a nodule prevalence in the indicator group > 10 % would suggest a community mf prevalence > 20 % with a sensitivity of 85 % and a specificity of 71 %. A multiple linear regression model of the arc-sine transformed mf prevalence in the village (all ages) on nodule prevalence in those aged > or = 15 years and altitude of the village explained 72 % of the variance. The model combining nodule and altitudinal information had a sensitivity of 92 % and a specificity of 71 % in comparison to an estimated mf prevalence of 21 % or more. It is suggested that the usefulness of the REA methods proposed be assessed in other areas of the Amazonian onchocerciasis focus.

The genome of Onchocerca volvulus, agent of river blindness

PubMed Central

Cotton, James A.; Bennuru, Sasisekhar; Grote, Alexandra; Harsha, Bhavana; Tracey, Alan; Beech, Robin; Doyle, Stephen R.; Dunn, Matthew; Dunning Hotopp, Julie C.; Holroyd, Nancy; Kikuchi, Taisei; Lambert, Olivia; Mhashilkar, Amruta; Mutowo, Prudence; Nursimulu, Nirvana; Ribeiro, Jose M. C.; Rogers, Matthew B.; Stanley, Eleanor; Swapna, Lakshmipuram S.; Tsai, Isheng J.; Unnasch, Thomas R.; Voronin, Denis; Parkinson, John; Nutman, Thomas B.; Ghedin, Elodie; Berriman, Matthew; Lustigman, Sara

2017-01-01

Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development. PMID:27869790

River-specific macrogenomic diversity in Simulium guianense s. l. (Diptera: Simuliidae), a complex of tropical American vectors associated with human onchocerciasis

PubMed Central

Hamada, Neusa; Cavalcante do Nascimento, Jeane Marcelle; Grillet, Maria Eugenia

2017-01-01

Simulium guianense Wise is a Latin American vector complex of black flies associated with transmission of the causal agent of human onchocerciasis (river blindness). An analysis of the chromosomal banding patterns of 607 larvae of S. guianense s. l. revealed a high level of variation involving 83 macrogenomic rearrangements across 25 populations in Brazil, French Guiana, and Venezuela. The 25 populations were assigned to 13 cytoforms (A1, A2, B1–B4, C, D, E1–E4, and F), some of which are probably valid species. Based on geographical proximity, a member of the B group of cytoforms probably represents the name-bearing type specimen of S. guianense and the primary vector in the last-remaining onchocerciasis foci in the Western Hemisphere. Cytoform B3 in Amapá State is implicated as an anthropophilic simuliid in an area currently and historically free of onchocerciasis. Distributions of cytoforms are associated with geography, elevation, and drainage basin, and are largely congruent with ecoregions. Despite extraordinarily large larval populations of S. guianense s. l. in big rivers and consequent production of female flies for dispersal, the cytoforms maintain their chromosomal distinction within individual rivers, suggesting a high degree of fidelity to the specialized breeding habitats—rocky shoals—of the natal rivers. PMID:28727841

River-specific macrogenomic diversity in Simulium guianense s. l. (Diptera: Simuliidae), a complex of tropical American vectors associated with human onchocerciasis.

PubMed

Adler, Peter H; Hamada, Neusa; Cavalcante do Nascimento, Jeane Marcelle; Grillet, Maria Eugenia

2017-01-01

Simulium guianense Wise is a Latin American vector complex of black flies associated with transmission of the causal agent of human onchocerciasis (river blindness). An analysis of the chromosomal banding patterns of 607 larvae of S. guianense s. l. revealed a high level of variation involving 83 macrogenomic rearrangements across 25 populations in Brazil, French Guiana, and Venezuela. The 25 populations were assigned to 13 cytoforms (A1, A2, B1-B4, C, D, E1-E4, and F), some of which are probably valid species. Based on geographical proximity, a member of the B group of cytoforms probably represents the name-bearing type specimen of S. guianense and the primary vector in the last-remaining onchocerciasis foci in the Western Hemisphere. Cytoform B3 in Amapá State is implicated as an anthropophilic simuliid in an area currently and historically free of onchocerciasis. Distributions of cytoforms are associated with geography, elevation, and drainage basin, and are largely congruent with ecoregions. Despite extraordinarily large larval populations of S. guianense s. l. in big rivers and consequent production of female flies for dispersal, the cytoforms maintain their chromosomal distinction within individual rivers, suggesting a high degree of fidelity to the specialized breeding habitats-rocky shoals-of the natal rivers.

The Cost of Annual versus Biannual Community-Directed Treatment of Onchocerciasis with Ivermectin: Ghana as a Case Study

PubMed Central

Turner, Hugo C.; Osei-Atweneboana, Mike Y.; Walker, Martin; Tettevi, Edward J.; Churcher, Thomas S.; Asiedu, Odame; Biritwum, Nana-Kwadwo; Basáñez, María-Gloria

2013-01-01

Background It has been proposed that switching from annual to biannual (twice yearly) mass community-directed treatment with ivermectin (CDTI) might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana. Methodology The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective. Principal Findings The estimated cost of treating annually was US Dollars (USD) 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round). The cost of CDTI was approximately 50–60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable. Conclusions/Significance This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control (or eliminate) onchocerciasis in Africa. PMID:24069497

Onchocerciasis in the Amazonian focus of southern Venezuela: altitude and blackfly species composition as predictors of endemicity to select communities for ivermectin control programmes.

PubMed

Vivas-Martinez, S; Basáñez, M G; Grillet, M E; Weiss, H; Botto, C; García, M; Villamizar, N J; Chavasse, D C

1998-01-01

In preparation for an ivermectin distribution programme, the prevalence and intensity of infection due to Onchocerca volvulus as well as the species composition and abundance of Simulium vectors were investigated in 22 Yanomami communities situated along 2 altitudinal transects in the southern Venezuelan onchocerciasis focus. These transects corresponded to the Ocamo-Putaco and Orinoco-Orinoquito river systems, covering a range of elevation between 50 m and 740 m above sea level (asl). A total of 831 people underwent parasitological examination in this survey and an additional 196 patients from a previous study, at an altitude of 950 m, were included in the analysis. A total of 92,659 man-biting blackflies were collected and identified to morphospecies. S. oyapockense s.l. was the predominant simuliid up to 150 m asl, whereas S. guianense s.l. and S. incrustatum s.l. prevailed above 150 m. Communities located below 150 m were found to range from hypo- to mesoendemic; all villages above 150 m proved to be hyperendemic (> 60% microfilarial prevalence) and mass ivermectin treatment should be implemented. Age above 10-14 years, altitude of the village and biting rate of S. guianense s.l. up to 200 m asl were found to be statistically significant independent predictors of infection by multivariate logistic regression using a spline model. There were no differences in infection status according to sex. Above 200 m, microfilarial rate and density remained approximately constant, prevalence averaging 79% regardless of blackfly abundance. For the implementation of ivermectin-based onchocerciasis control programmes in the Amazonian focus, altitude and species composition of the blackfly population might be adopted as useful indicators aiding selection of the most affected communities. However, below 200 m additional parasitological indicators may also be necessary. As a direct result of this study, regular mass-ivermectin delivery to meso- and hyperendemic communities is now in progress.

Onchocerca lupi causing ocular disease in two cats.

PubMed

Labelle, Amber L; Daniels, Joshua B; Dix, Michael; Labelle, Philippe

2011-09-01

Although canine ocular onchocerciasis has been well described as an emerging pathogen of dogs in Europe and North America over the past 20 years, there are no previous reports of feline ocular onchocerciasis. This report details the clinical, histopathologic, and molecular diagnosis of two domestic short hair cats residing in the United States infected with Onchocerca lupi causing episcleritis and orbital cellulitis. The results of this report suggest that O. lupi is a newly recognized disease of domestic cats. © 2011 American College of Veterinary Ophthalmologists.

Impact of vectorborne parasitic neglected tropical diseases on child health.

PubMed

Barry, Meagan A; Murray, Kristy O; Hotez, Peter J; Jones, Kathryn M

2016-07-01

Chagas disease, leishmaniasis, onchocerciasis and lymphatic filariasis are all vectorborne neglected tropical diseases (NTDs) that are responsible for significant disease burden in impoverished children and adults worldwide. As vectorborne parasitic diseases, they can all be targeted for elimination through vector control strategies. Examples of successful vector control programmes for these diseases over the past two decades have included the Southern Cone Initiative against Chagas disease, the Kala-azar Control Scheme against leishmaniasis, the Onchocerciasis Control Programme and the lymphatic filariasis control programme in The Gambia. A common vector control component in all of these programmes is the use of adulticides including dichlorodiphenyltrichloroethane and newer synthetic pyrethroid insecticides against the insect vectors of disease. Household spraying has been used against Chagas disease and leishmaniasis, and insecticide-treated bed nets have helped prevent leishmaniasis and lymphatic filariasis. Recent trends in vector control focus on collaborations between programmes and sectors to achieve integrated vector management that addresses the holistic vector control needs of a community rather than approaching it on a disease-by-disease basis, with the goals of increased efficacy, sustainability and cost-effectiveness. As evidence of vector resistance to currently used insecticide regimens emerges, research to develop new and improved insecticides and novel control strategies will be critical in reducing disease burden. In the quest to eliminate these vectorborne NTDs, efforts need to be made to continue existing control programmes, further implement integrated vector control strategies and stimulate research into new insecticides and control methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Transmission of Onchocerca volvulus by Simulium neavei in Mount Elgon Focus of Eastern Uganda Has Been Interrupted

PubMed Central

Katabarwa, Moses; Lakwo, Tom; Habomugisha, Peace; Agunyo, Stella; Byamukama, Edson; Oguttu, David; Ndyomugyenyi, Richard; Tukesiga, Ephraim; Ochieng, Galex Orukan; Abwaimo, Francis; Onapa, Ambrose; Lwamafa, Dennis W. K.; Walsh, Frank; Unnasch, Thomas R.; Richards, Frank O.

2014-01-01

The study determined that Simulium neavei-transmitted onchocerciasis in Mount Elgon onchocerciasis focus had been interrupted. Annual mass treatment with ivermectin changed to two times per year along with vector elimination in 2007. Then, baseline microfilaria (mf) prevalence data of 1994 in five sentinel communities were compared with follow-up data in 2005 and 2011. Blood spots from 3,051 children obtained in 2009 were analyzed for Onchocerca volvulus immunoglobulin G4 antibodies. Fresh water crab host captures and blackflies collected indicated their infestation with larval stages of S. neavei and presence or absence of the vector, respectively. Mf rates dropped from 62.2% to 0.5%, and 1 (0.03%) of 3,051 children was positive for O. volvulus antibodies. Crab infestation dropped from 41.9% in 2007 to 0%, and S. neavei biting reduced to zero. Both remained zero for the next 3 years, confirming interruption of onchocerciasis transmission, and interventions were halted. PMID:24686740

Prevalence of River Epilepsy in the Orientale Province in the Democratic Republic of the Congo

PubMed Central

Colebunders, Robert; Tepage, Floribert; Rood, Ente; Mandro, Michel; Abatih, Emmanuel Nji; Musinya, Gisele; Mambandu, Germain; Kabeya, José; Komba, Michel; Levick, Bethany; Mokili, John L; Laudisoit, Anne

2016-01-01

Background An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. Objective To determine the prevalence and distribution of epilepsy in an onchocerciasis endemic region in the Democratic Republic of the Congo (DRC). Design/Methods An epilepsy prevalence study was carried out in 2014, in two localities of the Bas-Uélé district, an onchocerciasis endemic region in the Orientale Province of the DRC. Risk factors for epilepsy were identified using a random effects logistic regression model and the distribution of epilepsy cases was investigated using the Moran’s I statistic of spatial auto-correlation. Results Among the 12,776 individuals of Dingila, 373 (2.9%) individuals with epilepsy were identified. In a house-to-house survey in Titule, 68 (2.3%) of the 2,908 people who participated in the survey were found to present episodes of epilepsy. Epilepsy showed a marked spatial pattern with clustering of cases occurring within and between adjacent households. Individual risk of epilepsy was found to be associated with living close to the nearest fast flowing river where blackflies (Diptera: Simuliidae)–the vector of Onchocerca volvulus–oviposit and breed. Conclusions The prevalence of epilepsy in villages in the Bas-Uélé district in the DRC was higher than in non-onchocerciasis endemic regions in Africa. Living close to a blackflies infested river was found to be a risk factor for epilepsy. PMID:27139245

Lymphatic Vascularisation and Involvement of Lyve-1+ Macrophages in the Human Onchocerca Nodule

PubMed Central

Attout, Tarik; Hoerauf, Achim; Dénécé, Gaëlle; Debrah, Alexander Yaw; Marfo-Debrekyei, Yeboah; Boussinesq, Michel; Wanji, Samuel; Martinez, Valérie; Mand, Sabine; Adjei, Ohene; Bain, Odile

2009-01-01

Onchocerciasis, caused by the filarial nematode Onchocerca volvulus, is a parasitic disease leading to debilitating skin disease and blindness, with major economic and social consequences. The pathology of onchocerciasis is principally considered to be a consequence of long-standing host inflammatory responses. In onchocerciasis a subcutaneous nodule is formed around the female worms, the core of which is a dense infiltrate of inflammatory cells in which microfilariae are released. It has been established that the formation of nodules is associated with angiogenesis. In this study, we show using specific markers of endothelium (CD31) and lymphatic endothelial cells (Lyve-1, Podoplanin) that not only angiogenesis but also lymphangiogenesis occurs within the nodule. 7% of the microfilariae could be found within the lymphatics, but none within blood vessels in these nodules, suggesting a possible route of migration for the larvae. The neovascularisation was associated with a particular pattern of angio/lymphangiogenic factors in nodules of onchocerciasis patients, characterized by the expression of CXCL12, CXCR4, VEGF-C, Angiopoietin-1 and Angiopoietin-2. Interestingly, a proportion of macrophages were found to be positive for Lyve-1 and some were integrated into the endothelium of the lymphatic vessels, revealing their plasticity in the nodular micro-environment. These results indicate that lymphatic as well as blood vascularization is induced around O. volvulus worms, either by the parasite itself, e.g. by the release of angiogenic and lymphangiogenic factors, or by consecutive host immune responses. PMID:20011036

New molecular identifiers for Simulium limbatum and Simulium incrustatum s.l. and the detection of genetic substructure with potential implications for onchocerciasis epidemiology in the Amazonia focus of Brazil.

PubMed

Conceição, Priscila A; Crainey, James L; Almeida, Tatiana P; Shelley, Anthony J; Luz, Sergio L B

2013-08-01

The Amazonia onchocerciasis focus of southern Venezuela and northern Brazil is the larger of the two remaining Latin American onchocerciasis foci where disease transmission still occurs and is often regarded as the most challenging of all the Latin American foci to eliminate onchocerciasis. The site is home to a population of over 20,000 semi-nomadic, hunter-gatherer Yanomami people and is made-up of a mosaic of rainforest and savannah ecologies, which are influenced by the area's undulating terrain and rich geological diversity. At least six blackfly vectors have been implicated in onchocerciasis transmission in this focus; however, because of the difficulty in their routine identification the relative importance of each has been obscured. Simulium limbatum and Simulium incrustatum s.l. have both been recorded as vectors in the Amazonia focus, but they are difficult to discriminate morphologically and thus the ecological range of these species, and indeed the presence of S. limbatum in the Amazonia focus at all, have remained controversial. In the work described here, we report 15 S. incrustatum s.l. CO1 sequences and 27 S. limbatum sequences obtained from field-caught adult female blackflies collected from forest and savannah localities, inside and just outside the Amazonia focus. Phylogenetic analysis with the sequences generated in this study, showed that both the S. limbatum and the S. incrustatum s.l. CO1 sequences obtained (even from specimens living in sympatry) all fell into discrete species-specific bootstrap-supported monophyletic groups and thus confirmed the utility of the CO1 gene for identifying both these species inside the Amazonia focus. As the S. limbatum-exclusive cluster included CO1 sequences obtained from forest-caught and morphologically identified specimens these results provide the clearest evidence yet of the presence of S. limbatum inside the Amazonia focus. The question, however, of whether S. limbatum is actually a vector in the focus still remains unanswered as the data presented here also suggest that S. limbatum found in the savannahs adjacent to, but outside the Amazonia focus (and which represent the only S. limbatum population to be unambiguously incriminated as a host of Onchocerca volvulus), are genetically distinct from those living inside the focus. These findings highlight the need for a clearer picture of the vector taxonomy inside the Amazonia onchocerciasis focus. Copyright © 2013 Elsevier B.V. All rights reserved.

Neglected Tropical Diseases outside the Tropics

PubMed Central

Norman, Francesca F.; Pérez de Ayala, Ana; Pérez-Molina, José-Antonio; Monge-Maillo, Begoña; Zamarrón, Pilar; López-Vélez, Rogelio

2010-01-01

Background The neglected tropical diseases (NTDs) cause significant morbidity and mortality worldwide. Due to the growth in international travel and immigration, NTDs may be diagnosed in countries of the western world, but there has been no specific focus in the literature on imported NTDs. Methods Retrospective study of a cohort of immigrants and travelers diagnosed with one of the 13 core NTDs at a Tropical Medicine Referral Unit in Spain during the period April 1989-December 2007. Area of origin or travel was recorded and analyzed. Results There were 6168 patients (2634 immigrants, 3277 travelers and 257 VFR travelers) in the cohort. NTDs occurred more frequently in immigrants, followed by VFR travelers and then by other travelers (p<0.001 for trend). The main NTDs diagnosed in immigrants were onchocerciasis (n = 240, 9.1%) acquired mainly in sub-Saharan Africa, Chagas disease (n = 95, 3.6%) in immigrants from South America, and ascariasis (n = 86, 3.3%) found mainly in immigrants from sub-Saharan Africa. Most frequent NTDs in travelers were: schistosomiasis (n = 43, 1.3%), onchocerciasis (n = 17, 0.5%) and ascariasis (n = 16, 0.5%), and all were mainly acquired in sub-Saharan Africa. The main NTDs diagnosed in VFR travelers were onchocerciasis (n = 14, 5.4%), and schistosomiasis (n = 2, 0.8%). Conclusions The concept of imported NTDs is emerging as these infections acquire a more public profile. Specific issues such as the possibility of non-vectorial transmission outside endemic areas and how some eradication programmes in endemic countries may have an impact even in non-tropical western countries are addressed. Recognising NTDs even outside tropical settings would allow specific prevention and control measures to be implemented and may create unique opportunities for research in future. PMID:20668546

“Test and not treat” for onchocerciasis control in a Loa loa endemic area

PubMed Central

Kamgno, Joseph; Pion, Sébastien D.; Chesnais, Cédric B.; Bakalar, Matthew H.; D'Ambrosio, Michael V.; Mackenzie, Charles D.; Nana-Djeunga, Hugues C.; Gounoue-Kamkumo, Raceline; Njitchouang, Guy-Roger; Nwane, Philippe; Tchatchueng-Mbouga, Jules B.; Wanji, Samuel; Stolk, Wilma A.; Fletcher, Daniel A.; Klion, Amy D.; Nutman, Thomas B.; Boussinesq, Michel

2017-01-01

Background Implementation of ivermectin-based community treatment for onchocerciasis or lymphatic filariasis elimination has been delayed in Central Africa because of severe adverse events (SAEs), including death, in people with high levels of circulating Loa loa microfilariae (mf). LoaScope, a rapid field-friendly diagnostic tool to quantify L. loa mf in peripheral blood, permits point-of-care identification of individuals “at risk” for SAEs. Methods A “Test and not Treat” (TaNT) strategy was used to implement ivermectin treatment in the Okola health district in Cameroon, where ivermectin distribution was halted in 1999 after the occurrence of fatal Loa-related SAEs. The LoaScope was used to identify and exclude individuals with >20,000 mf per milliliter of blood (at-risk for SAEs) from ivermectin treatment. Active surveillance for post-treatment adverse events (AEs) was conducted daily for 7 days. Results Between August and October 2015, 16,259 (71.1%) individuals >=5 years of age were tested out of a target population of ~22,800. Among the ivermectin-eligible population, 15,522 (95.5%) received ivermectin; 340 (2.1%) were excluded from ivermectin treatment because of a L. loa density above the risk-threshold and 397 (2.4%) were excluded for pregnancy or illness. No SAEs were observed. Non-severe AEs were recorded in 934 individuals, most (67%) of whom had no detectable L. loa mf. Conclusions The LoaScope-based TaNT strategy permitted safe re-implementation of community-wide ivermectin distribution in a heretofore ‘off limits’ health district in Cameroon and is an extremely promising and practical approach for large-scale ivermectin treatment for lymphatic filariasis and onchocerciasis elimination in Loa loa-endemic areas. PMID:29116890

The varied beneficial effects of ivermectin (Mectizan) treatment, as observed within onchocerciasis foci in south-eastern Nigeria.

PubMed

Anosike, J C; Dozie, I N S; Ameh, G I; Ukaga, C N; Nwoke, B E B; Nzechukwu, C T; Udujih, O S; Nwosu, D C

2007-10-01

In the treatment of humans, ivermectin (Mectizan((R))), a semi-synthetic macrocyclic lactone, is now primarily used as a rapid microfilaricide. The drug has several other benefits, however, and these have recently been investigated in five states in south-eastern Nigeria, where there have been mass treatments with ivermectin, for the control of Onchocerca volvulus, for more than 10 years. Between the January and December of 2005, 3125 adult onchocerciasis patients (each aged >/=20 years and known to have at least one clinical sign of onchocerciasis) were enlisted, clinically examined and interviewed. Relevant data were collected in the interviews, using a structured, pre-tested questionnaire, and in personal and focus-group discussions. Overall, 612 (19.6%) of the subjects reported that they had had nodules that had disappeared following repeated doses of ivermectin, although only 83.8% of the 612 attributed their nodule clearance to ivermectin (the other 16.2% being unsure of the cause). A larger percentage of the subjects (24.6%) reported that they had expelled intestinal helminths following the last round of ivermectin treatment (i.e. been dewormed). Other side-benefits reported in the study were improved vision (11.7% of subjects), reversal of secondary amenorrhea (4.5%), increased appetite (22.3%), reduction in arthritic or other musculo-skeletal pain (7.9%), reductions in the severity of body itching (18.5%) and skin rash (17.3%), darkening of leopard skin (6.6%), improved libido in men (6.6%), and clearance of head lice (4.5%). If, via health education, the local communities could be made more aware of the side-benefits of ivermectin treatment, the sustainability of the on-going programme of community-directed treatment with ivermectin (CDTI) in south-eastern Nigeria would probably be improved.

Structure of the microfilarial reservoir of Loa loa in the human host and its implications for monitoring the progr,ammes of Community-Directed Treatment with Ivermectin carried out in Africa.

PubMed

Pion, D S S; Gardon, J; Kamgno, J; Gardon-Wendel, N; Chippaux, J P; Boussinesq, M

2004-11-01

This paper describes the structure of the microfilarial reservoir of Loa loa in an endemic population of central Cameroon. The possible effects of age and sex on the prevalence and intensity of microfilaraemia have been explored. Logistic analysis showed that the prevalence of microfilaraemia increased significantly with age, reaching 60 % in the oldest males. This result suggests that the figure commonly reported, according to which only one third of the infected individuals were microfilaraemic, should be reconsidered; in addition, as part of surveys of loiasis, crude microfilaraemia prevalence values should be replaced by adjusted ones. The intensity of infection did not show any age-specific change. As a result, even if the oldest members of the male population are clearly the most at risk of developing post-ivermectin serious adverse reactions, especially Loa-encephalopathy, the other members of the population are not risk-free. Therefore, in those areas where the African Programme for Onchocerciasis Control is undertaking regular mass distributions of ivermectin for onchocerciasis control, and where loiasis is co-endemic, no subpopulation should be excluded from surveillance and monitoring during community directed treatments with ivermectin.

Prevention and control of neglected tropical diseases: overview of randomized trials, systematic reviews and meta-analyses

PubMed Central

Kappagoda, Shanthi

2014-01-01

Abstract Objective To analyse evidence from randomized controlled trials (RCTs) on the prevention and control of neglected tropical diseases (NTDs) and to identify areas where evidence is lacking. Methods The Cochrane Central Register of Controlled Trials and PubMed were searched for RCTs and the Cochrane Database of Systematic Reviews and PubMed were searched for meta-analyses and systematic reviews, both from inception to 31 December 2012. Findings Overall, 258 RCTs were found on American trypanosomiasis, Buruli ulcer, dengue, geohelminth infection, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis or trachoma. No RCTs were found on cysticercosis, dracunculiasis, echinococcosis, foodborne trematodes, or human African trypanosomiasis. The most studied diseases were geohelminth infection (51 RCTs) and leishmaniasis (46 RCTs). Vaccines, chemoprophylaxis and interventions targeting insect vectors were evaluated in 113, 99 and 39 RCTs, respectively. Few addressed how best to deliver preventive chemotherapy, such as the choice of dosing interval (10) or target population (4), the population coverage needed to reduce transmission (2) or the method of drug distribution (1). Thirty-one publications containing 32 systematic reviews (16 with and 16 without meta-analyses) were found on American trypanosomiasis, dengue, geohelminths, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis or trachoma. Together, they included only 79 of the 258 published RCTs (30.6%). Of 36 interventions assessed, 8 were judged effective in more than one review. Conclusion Few RCTs on the prevention or control of the principal NTDs were found. Trials on how best to deliver preventive chemotherapy were particularly rare. PMID:24839325

In sickness or in health: TDR's partners. 6. The French Development Research Institute (ORSTOM).

PubMed

1997-10-01

One of the partner agencies working with the UN Development Program/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases (TDR) is the French development research agency, ORSTOM. ORSTOM has been conducting research in intertropical regions for approximately 50 years with a particular focus on entomoparasitological aspects of vector-borne diseases. ORSTOM's close collaboration with TDR since the TDR Special Program was launched in 1975 has led to 1) improved knowledge about various aspects of trypanosomiasis that allowed identification of ways to control the epidemic; 2) reappraisal of the taxonomy of the parasitic protozoa responsible for Chagas disease and leishmaniasis; 3) improvements in the strategy to fight malaria; 4) assessment of the efficacy of ivermectin as a form of mass treatment for onchocerciasis; 5) improved knowledge about dracunculiasis that contributed to an eradication campaign; 6) expansion of the scope of biological control of bancroftian filariasis and other parasites; and 7) improved knowledge about ways to control two schistosome species. ORSTOM also participated in a training and structural enhancement initiative that resulted in creation of the Boake Medical and Veterinary Entomology Training Center. ORSTOM is currently undergoing a complete restructuring to respond to changes in international tropical disease research and to changing priorities that focus on vector-borne diseases, nutrition, AIDS, and health systems.

Overcoming the challenges of drug discovery for neglected tropical diseases: the A·WOL experience.

PubMed

Johnston, Kelly L; Ford, Louise; Taylor, Mark J

2014-03-01

Neglected tropical diseases (NTDs) are a group of 17 diseases that typically affect poor people in tropical countries. Each has been neglected for decades in terms of funding, research, and policy, but the recent grouping of them into one unit, which can be targeted using integrated control measures, together with increased advocacy has helped to place them on the global health agenda. The World Health Organization has set ambitious goals to control or eliminate 10 NTDs by 2020 and launched a roadmap in January 2012 to guide this global plan. The result of the launch meeting, which brought together representatives from the pharmaceutical industry, donors, and politicians, was the London Declaration: a series of commitments to provide more drugs, research, and funds to achieve the 2020 goals. Drug discovery and development for these diseases are extremely challenging, and this article highlights these challenges in the context of the London Declaration, before focusing on an example of a drug discovery and development program for the NTDs onchocerciasis and lymphatic filariasis (the anti-Wolbachia consortium, A·WOL).

The esperanza window trap reduces the human biting rate of Simulium ochraceum s.l. in formerly onchocerciasis endemic foci in Southern Mexico.

PubMed

Rodríguez-Pérez, Mario A; Garza-Hernández, Javier A; Salinas-Carmona, Mario C; Fernández-Salas, Ildefonso; Reyes-Villanueva, Filiberto; Real-Najarro, Olga; Cupp, Eddie W; Unnasch, Thomas R

2017-07-01

The Esperanza Window Trap (EWT) baited with CO2 and human sweat compounds is attractive to Simulium ochraceum s.l., the primary vector of Onchocerca volvulus in the historically largest endemic foci in México and Guatemala. The ability of the EWT to locally reduce numbers of questing S. ochraceum s.l. was evaluated in two formerly onchocerciasis endemic communities in Southern México. At each community, two EWTs were placed in or near a school or household and flies were collected sequentially for a total of 10 days. Black fly collections were then carried out for an additional 10 days in the absence of the EWTs. Flies were also collected outside the dwellings to control for variations in the local fly populations. When the EWTs were present, there was a significant reduction in the human biting rate at both the household and school locations at collection sites, with a greater effect observed in the schools. These results indicate that the EWTs not only have potential as a black fly monitoring tool but may be used for reducing personal exposure to fly bites in Mesoamerica.

Nodding syndrome since 2012: recent progress, challenges and recommendations for future research.

PubMed

Colebunders, R; Post, R; O'Neill, S; Haesaert, G; Opar, B; Lakwo, T; Laudisoit, A; Hendy, A

2015-02-01

We aim to review the current epidemiology of nodding syndrome (NS) and discuss relevant gaps in research. NS and convulsive epilepsy of unknown aetiology are clustered within the same villages and families in onchocerciasis-endemic areas. They are therefore potentially different clinical expressions of the same disease. It has been difficult to perform full autopsies on NS patients who die in remote villages. Adequate fixation of tissue immediately after death is critical for the examination of brain tissue. Therefore, post-mortem transsphenoidal brain biopsies, performed immediately after death by trained nurses, will provide the best option for obtaining tissue for analysis. We suspect that certain blackflies in onchocerciasis-endemic areas may transmit a novel pathogen that could cause NS and epilepsy. This is supported by a recent drop in the number of new NS cases coinciding with vector control activities aimed at reducing blackfly populations in northern Uganda. We propose that metagenomic studies of human samples, blackflies and microfilariae are conducted to screen for pathogens, and that a clinical trial is planned to evaluate the impact of larviciding against NS and epilepsy epidemics. © 2014 John Wiley & Sons Ltd.

Evolution, epidemiology, and population genetics of black flies (Diptera: Simuliidae).

PubMed

Adler, Peter H; Cheke, Robert A; Post, Rory J

2010-10-01

More than 2000 species of black flies feed on vertebrate blood; 1.5% of all species are vectors of pathogens that cause human diseases. Of nine simuliid-borne animal diseases, only two, mansonellosis and onchocerciasis, afflict humans. Onchocerciasis is a debilitating disease infecting an estimated 40 million people in Africa, Latin America, and Yemen, whereas mansonellosis is a mild disease in the Neotropics. Cytogenetic studies of natural populations of more than 500 species of black flies have revealed that the classic morphospecies of taxonomists is typically a complex of two or more reproductively isolated entities, or sibling (cryptic) species. Most vectors of human pathogens are sibling species, each ecologically unique in traits such as breeding habitats, dispersal capabilities, and degree of vector competence. We review the evolution of black flies, the cytogenetics that have revealed about 260 cytologically distinct entities, the molecular studies that continue to expose additional hidden biodiversity, and a case study of the epidemiology of the Simulium damnosum complex, the largest species complex of blood-feeding arthropods on Earth and the premier group of black flies responsible for human onchocerciasis. Copyright 2010 Elsevier B.V. All rights reserved.

Impact of five annual rounds of mass drug administration with ivermectin on onchocerciasis in Sierra Leone.

PubMed

Koroma, Joseph B; Sesay, Santigie; Conteh, Abdul; Koudou, Benjamin; Paye, Jusufu; Bah, Mohamed; Sonnie, Mustapha; Hodges, Mary H; Zhang, Yaobi; Bockarie, Moses J

2018-04-06

Onchocerciasis is endemic in 12 of the 14 health districts of Sierra Leone. Good treatment coverage of community-directed treatment with ivermectin was achieved between 2005 and 2009 after the 11-year civil conflict. Sentinel site surveys were conducted in 2010 to evaluate the impact of five annual rounds of ivermectin distribution. In total, 39 sentinel villages from hyper- and meso-endemic areas across the 12 endemic districts were surveyed using skin snips in 2010. Results were analyzed and compared with the baseline data from the same 39 villages. The average microfilaridermia (MF) prevalence across 39 sentinel villages was 53.10% at baseline. The MF prevalence was higher in older age groups, with the lowest in the age group of 1-9 years (11.00%) and the highest in the age group of 40-49 years (82.31%). Overall mean MF density among the positives was 28.87 microfilariae (mf)/snip, increasing with age with the lowest in the age group of 1-9 years and the highest in the age group of 40-49 years. Males had higher MF prevalence and density than females. In 2010 after five rounds of mass drug administration, the overall MF prevalence decreased by 60.26% from 53.10% to 21.10%; the overall mean MF density among the positives decreased by 71.29% from 28.87 mf/snip to 8.29 mf/snip; and the overall mean MF density among all persons examined decreased by 88.58% from 15.33 mf/snip to 1.75 mf/snip. Ten of 12 endemic districts had > 50% reduction in MF prevalence. Eleven of 12 districts had ≥50% reduction in mean MF density among the positives. A significant reduction of onchocerciasis MF prevalence and mean density was recorded in all 12 districts of Sierra Leone after five annual MDAs with effective treatment coverage. The results suggested that the onchocerciasis elimination programme in Sierra Leone was on course to reach the objective of eliminating onchocerciasis in the country by the year 2025. Annual MDA with ivermectin should continue in all 12 districts and further evaluations are needed across the country to assist the NTDP with programme decision making.

Interruption of Onchocerca volvulus transmission in Northern Venezuela.

PubMed

Convit, Jacinto; Schuler, Harland; Borges, Rafael; Olivero, Vimerca; Domínguez-Vázquez, Alfredo; Frontado, Hortencia; Grillet, María E

2013-10-07

Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10-12 years of 6-monthly Mectizan (ivermectin) treatment to all the eligible residents. In-depth entomologic and epidemiologic surveys were serially conducted from 2001-2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. From 2007-2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children < 15 years-old demonstrated that 0 out of 6,590 individuals were harboring antibodies to Ov-16. Finally, epidemiological surveys made during 2010 (NC) and 2012 (NE) showed no evidence of microfilariae in the skin and eyes of the population. These results meet the WHO criteria for absence of parasite transmission and disease morbidity in these endemic areas which represent 91% of the population previously at-risk in the country. Consequently, the two Northern foci are currently under post-treatment onchocerciasis surveillance status in Venezuela.

Interruption of Onchocerca volvulus transmission in Northern Venezuela

PubMed Central

2013-01-01

Background Onchocerciasis is caused by Onchocerca volvulus and transmitted by Simulium species (black flies). In the Americas, the infection has been previously described in 13 discrete regional foci distributed among six countries (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela) where more than 370,000 people are currently considered at risk. Since 2001, disease control in Venezuela has relied on the mass drug administration to the at-risk communities. This report provides empirical evidence of interruption of Onchocerca volvulus transmission by Simulium metallicum in 510 endemic communities from two Northern foci of Venezuela, after 10–12 years of 6-monthly Mectizan® (ivermectin) treatment to all the eligible residents. Methods In-depth entomologic and epidemiologic surveys were serially conducted from 2001–2012 in selected (sentinel and extra-sentinel) communities from the North-central (NC) and North-east (NE) onchocerciasis foci of Venezuela in order to monitor the impact of ivermectin treatment. Results From 2007–2009, entomological indicators in both foci confirmed that 0 out of 112,637 S. metallicum females examined by PCR contained L3 infection in insect heads. The upper bound of the 95% confidence intervals of the infective rate of the vector reached values below 1% by 2009 (NC) and 2012 (NE). Additionally, after 14 (NC) and 22 (NE) rounds of treatment, the seasonal transmission potential (±UL CIs) of S. metallicum was under the critical threshold of 20 L3 per person per season. Serological analysis in school children < 15 years-old demonstrated that 0 out of 6,590 individuals were harboring antibodies to Ov-16. Finally, epidemiological surveys made during 2010 (NC) and 2012 (NE) showed no evidence of microfilariae in the skin and eyes of the population. Conclusions These results meet the WHO criteria for absence of parasite transmission and disease morbidity in these endemic areas which represent 91% of the population previously at-risk in the country. Consequently, the two Northern foci are currently under post-treatment onchocerciasis surveillance status in Venezuela. PMID:24499653

Elimination and eradication of neglected tropical diseases with mass drug administrations: a survey of experts.

PubMed

Keenan, Jeremy D; Hotez, Peter J; Amza, Abdou; Stoller, Nicole E; Gaynor, Bruce D; Porco, Travis C; Lietman, Thomas M

2013-01-01

Lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma are the five most prevalent neglected tropical diseases in the world, and each is frequently treated with mass drug administrations. We performed a survey of neglected tropical diseases experts to elicit their opinions on the role of mass drug administrations for the elimination of these infections. We sent an online survey to corresponding authors who had published an article about a neglected tropical disease from 2007 to 2011. Of 825 unique authors who were invited to complete the survey, 365 (44.2%) responded, including 234 (28.4%) who answered questions regarding one of the five most prevalent neglected tropical diseases. Respondents had varying opinions about the goals of programmatic activities for their chosen neglected tropical disease, with elimination or eradication identified as the most important goal by 87% of lymphatic filariasis respondents, 66% of onchocerciasis respondents, 55% of trachoma respondents, 24% of schistosomiasis respondents, and 21% of soil-transmitted helminth respondents. Mass drug administrations, other non-medication health measures, and education were generally thought to be more important for elimination than vector control, development of a new tool, or the presence of a secular trend. Drug resistance was thought to be a major limitation of mass drug administrations for all five neglected tropical diseases. Over half of respondents for lymphatic filariasis and trachoma thought that repeated mass drug administrations could eliminate infection within ten years of the initiation of mass treatments. Respondents for lymphatic filariasis, onchocerciasis, and trachoma were more enthusiastic about the prospects of elimination and eradication than were respondents for schistosomiasis or soil-transmitted helminths. Mass drug administrations were generally believed to be among the most important factors for the success of elimination efforts for each of the five neglected tropical diseases, highlighting the opportunity for integrating drug distributions.

Interruption of the transmission of Onchocerca volvulus in the Kashoya-Kitomi focus, western Uganda by long-term ivermectin treatment and elimination of the vector Simulium neavei by larviciding.

PubMed

Lakwo, T; Garms, R; Wamani, J; Tukahebwa, E M; Byamukama, E; Onapa, A W; Tukesiga, E; Katamanywa, J; Begumisa, S; Habomugisha, P; Oguttu, D; Byamukama, E; Richards, F; Unnasch, T R; Katabarwa, M

2017-03-01

Uganda is the only country in sub-Saharan Africa whose onchocerciasis elimination programme extensively uses vector control and biannual treatment with ivermectin. The purpose of this study was to assess the impact of combined strategies on interrupting onchocerciasis transmission in the Kashoya-Kitomi focus. Mass Drug Administration annually (13 years) followed by biannual treatments (6 years) and ground larviciding (36 cycles in 3 years) with temephos (Abate ® , EC500) against Simulium neavei were conducted. Routine fly catches were conducted for over seven years in six catching sites and freshwater crabs Potamonautes aloysiisabaudiae were examined for immature stages of Simulium neavei. Epidemiological assessments by skin snip were performed in 2004 and 2013. Collection of dry blood spots (DBS) from children <10 years for IgG4 antibodies analysis were done in 2010 and 2013. Treatment coverage with ivermectin improved with introduction of biannual treatment strategy. Microfilaria prevalence reduced from 85% in 1991 to 62% in 2004; and to only 0.5% in 2013. Crab infestation reduced from 59% in 2007 to 0% in 2013 following ground larviciding. Comparison of total fly catches before and after ground larviciding revealed a drop from 5334 flies in 2007 to 0 flies in 2009. Serological assays conducted among 1,362 children in 2010 revealed 11 positive cases (0.8%; 95% CI: 0.4%-1.2%). However, assessment conducted on 3246 children in 2013 revealed five positives, giving point prevalence of 0.15%; 95% CI: 0.02%-0.28%. Four of the five children subjected to O-150 PCR proved negative. The data show that transmission of onchocerciasis has been interrupted based on national and WHO Guidelines of 2012 and 2016, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Human anthelminthic vaccines: Rationale and challenges.

PubMed

Hotez, Peter J; Strych, Ulrich; Lustigman, Sara; Bottazzi, Maria Elena

2016-06-24

Helminth infections are the most common afflictions of humankind, affecting almost every single person living in profound poverty. Through mass drug administration (MDA) we have seen sharp declines in the global prevalence of some helminth infections, including lymphatic filariasis, onchocerciasis, and ascariasis. However, since 1990, there has been no appreciable decrease in the global prevalence of hookworm infection, schistosomiasis, or food-borne trematodiases. Through the activities of a non-profit product development partnerships and two research institutes, a total of five human anthelmintic vaccines for hookworm infection (two) and schistosomiasis (three) have advanced from discovery through manufacture and are now in Phase 1 clinical testing. At least three additional antigens, including two for onchocerciasis and one for schistosomiasis, are also advancing through preclinical development with the intention of moving into the clinic soon. These preventive human anthelmintic vaccines could be used as stand-alone technologies administered to infants as part of the Expanded Program on Immunization (EPI), or together with anthelmintic drugs in programs linked to MDA. Significant hurdles though could hinder the advancement of these vaccines into later-stage clinical and product development and licensure. They include the absence of a major pharma partner (and the resultant access to adjuvants and industrial scale manufacturing expertise), an uncharted roadmap for how to introduce anthelmintic vaccines into appropriate health systems, uncertain global access and regulatory strategies that might need to rely on developing country vaccine manufacturers and national regulatory authorities, and the lack of innovative financing schemes. However, the public health and economic benefits of introducing these vaccines could be massive and therefore deserve international attention and support. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors affecting the attrition of community-directed distributors of ivermectin, in an onchocerciasis-control programme in the Imo and Abia states of south-eastern Nigeria.

PubMed

Emukah, E C; Enyinnaya, U; Olaniran, N S; Akpan, E A; Hopkins, D R; Miri, E S; Amazigo, U; Okoronkwo, C; Stanley, A; Rakers, L; Richards, F O; Katabarwa, M N

2008-01-01

In areas of Nigeria where onchocerciasis is endemic, community-directed distributors (CDD) distribute ivermectin annually, as part of the effort to control the disease. Unfortunately, it has been reported that at least 35% of the distributors who have been trained in Nigeria are unwilling to participate further as CDD. The selection and training of new CDD, to replace those unwilling to continue, leads to annual expense that the national onchocerciasis-programme is finding difficult to meet, given other programme priorities and the limited resources. If the reported levels of attrition are true, they seriously threaten the sustainability of community-directed treatment with ivermectin (CDTI) in Nigeria. In 2002, interviews were held with 101 people who had been trained as CDD, including those who had stopped serving their communities, from 12 communities in south-eastern Nigeria that had high rates of CDD attrition. The results showed that, although the overall reported CDD attrition was 40.6%, the actual rate was only 10.9%. The CDD who had ceased participating in the annual rounds of ivermectin blamed a lack of incentives (65.9%), the demands of other employment (14.6%), the long distances involved in the house-to-house distribution (12.2%) or marital duties (7.3%). Analysis of the data obtained from all the interviewed CDD showed that inadequate supplies of ivermectin (P<0.01), lack of supervision (P<0.05) and a lack of monetary incentives (P<0.001) led to significant increases in attrition. Conversely, CDD retention was significantly enhanced when the distributors were selected by their community members (P<0.001), supervised (P<0.001), supplied with adequate ivermectin tablets (P<0.05), involved in educating their community members (P<0.05), and/or involved in other health programmes (P<0.001). Although CDD who were involved in other health programmes were relatively unlikely to cease participating in the distributions, they were more likely to take longer than 14 days to complete ivermectin distribution than other CDD, who only distributed ivermectin. Data obtained in interviews with present and past CDD appear vital for informing, directing, protecting and enhancing the performance of CDTI programmes, in Nigeria and elsewhere.

Elimination of onchocerciasis in Ecuador: findings of post-treatment surveillance.

PubMed

Guevara, Ángel; Lovato, Raquel; Proaño, Roberto; Rodriguez-Perez, Mario A; Unnasch, Thomas; Cooper, Philip J; Guderian, Ronald H

2018-04-24

The Esmeraldas focus of onchocerciasis in Ecuador expanded geographically during the 1980s and was associated with severe ocular and skin disease. Mass drug administration (MDA) with ivermectin started in 1991, initially once but later twice a year, in the principle endemic focus followed by all satellite foci. Treatment was stopped in 2009 when entomological assessments determined that transmission of Onchocerca volvulus had been interrupted. Three years after the cessation of ivermectin treatment in 2012, as defined by the WHO guidelines for onchocerciasis elimination, blackfly collections were done in four sentinel sites in former hyperendemic areas. The presence of infective larvae in local vectors, Simulium exiguum and Simulum quadrivittatum, was assessed by detection of O. volvulus DNA by PCR. Additional flies captured in four extra-sentinel sites located in former hyper- and mesoendemic dispersed isolated areas were also assessed. The results from 68,310 captured blackflies, 40,114 from four sentinel villages in the previously hyperendemic areas (Corriente Grande, El Tigre, San Miguel on Río Cayapas and Naranjal on Río Canandé) and 28,197 from extra-sentinel locations, were all negative for the presence of O. volvulus. These extra-sentinel sites (Hualpí on Río Hoja Blanca, Capulí on Río Onzole, La Ceiba on Río Tululví and Medianía on Río Verde) were included to provide additional evidence of the impact of MDA on the transmission of O. volvulus in isolated endemic areas. Our data indicate that transmission of O. volvulus has been stopped in all endemic areas in Ecuador, including all satellite foci outside the main focus. These findings indicate that a strategy of ivermectin distribution twice a year to over 85% of the treatment-eligible population was effective in eliminating the infection from Ecuador in a focus with a highly competent primary vector, S. exiguum, and where the infection rates were equal to or greater than observed in many onchocerciasis foci in Africa.

New tools and insights to assist with the molecular identification of Simulium guianense s.l., main Onchocerca volvulus vector within the highland areas of the Amazonia onchocerciasis focus.

PubMed

Crainey, James L; Mattos-Glória, Aline; Hamada, Neusa; Luz, Sérgio L B

2014-03-01

Following the success of the Onchocerciasis Elimination Programme for the Americas (OEPA), there is now just one Latin American onchocerciasis focus where onchocerciasis transmission is described as 'on-going:' the Amazonia Onchocerciasis focus. In the hyperendemic highland areas of the Amazonia focus, Simulium guianense s.l. Wise are the most important vectors of the disease. Populations of S. guianense s.l. are, however, known to vary in their cytogenetics and in a range of behaviours, including in their biting habits. In the hypoendemic lowland areas of the Amazonia focus, for example, S. guianense s.l. are generally regarded as zoophilic and consequently unimportant to disease transmission. Robust tools, to discriminate among various populations of S. guianense s.l. have, however, not yet been developed. In the work reported here, we have assessed the utility of a ribosomal DNA sequence fragment spanning the nuclear ribosomal ITS-1, ITS-2 and 5.8S sequence regions and a ∼850 nucleotide portion of the mitochondrial cytochrome oxidase gene (CO1) for species-level identification and for resolving the within species substructuring. We report here how we have generated 78 CO1 sequences from a rich set of both zoophilic and anthropophilic populations of S. guianense s.l. that were collected from eight sites that are broadly distributed across Brazil. Consistent with previous findings, our analysis supports the genetic isolation of Simulium litobranchium from S. guianense s.l. In contrast with previous findings, however, our results did not provide support for the divergence of the two species prior to the radiation of S. guianense s.l. In our analysis of the S. guianense s.l. ribosomal DNA sequence trace files we generated, we provide clear evidence of multiple within-specimen single nucleotide polymorphisms and indels suggesting that S. guianense s.l. ribosomal DNA is not a good target for conventional DNA barcoding. This is the first report of S. guianense s.l. within individual ribosomal DNA variation and thus the first evidence that the species is not subject to the normal effects of concerted evolution. Collectively, these data illustrate the need for diverse sampling in the development of robust molecular tools for vector identification and suggest that ribosomal DNA might be able to assist with resolving S. guianense s.l. species substructuring that C01 barcoding has hitherto failed to. Copyright © 2013 Elsevier B.V. All rights reserved.

A Recombinant Positive Control for Serology Diagnostic Tests Supporting Elimination of Onchocerca volvulus.

PubMed

Golden, Allison; Stevens, Eric J; Yokobe, Lindsay; Faulx, Dunia; Kalnoky, Michael; Peck, Roger; Valdez, Melissa; Steel, Cathy; Karabou, Potochoziou; Banla, Méba; Soboslay, Peter T; Adade, Kangi; Tekle, Afework H; Cama, Vitaliano A; Fischer, Peter U; Nutman, Thomas B; Unnasch, Thomas R; de los Santos, Tala; Domingo, Gonzalo J

2016-01-01

Serological assays for human IgG4 to the Onchocerca volvulus antigen Ov16 have been used to confirm elimination of onchocerciasis in much of the Americas and parts of Africa. A standardized source of positive control antibody (human anti-Ov16 IgG4) will ensure the quality of surveillance data using these tests. A recombinant human IgG4 antibody to Ov16 was identified by screening against a synthetic human Fab phage display library and converted into human IgG4. This antibody was developed into different positive control formulations for enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT) platforms. Variation in ELISA results and utility as a positive control of the antibody were assessed from multiple laboratories. Temperature and humidity conditions were collected across seven surveillance activities from 2011-2014 to inform stability requirements for RDTs and positive controls. The feasibility of the dried positive control for RDT was evaluated during onchocerciasis surveillance activity in Togo, in 2014. When the anti-Ov16 IgG4 antibody was used as a standard dilution in horseradish peroxidase (HRP) and alkaline phosphatase (AP) ELISAs, the detection limits were approximately 1ng/mL by HRP ELISA and 10ng/mL by AP ELISA. Positive control dilutions and spiked dried blood spots (DBS) produced similar ELISA results. Used as a simple plate normalization control, the positive control antibody may improve ELISA data comparison in the context of inter-laboratory variation. The aggregate temperature and humidity monitor data informed temperature parameters under which the dried positive control was tested and are applicable inputs for testing of diagnostics tools intended for sub-Saharan Africa. As a packaged positive control for Ov16 RDTs, stability of the antibody was demonstrated for over six months at relevant temperatures in the laboratory and for over 15 weeks under field conditions. The recombinant human anti-Ov16 IgG4 antibody-based positive control will benefit inter-laboratory validation of ELISA assays and serve as quality control (QC) reagents for Ov16 RDTs at different points of the supply chain from manufacturer to field use.

Detection of Onchocerca volvulus in Skin Snips by Microscopy and Real-Time Polymerase Chain Reaction: Implications for Monitoring and Evaluation Activities.

PubMed

Thiele, Elizabeth A; Cama, Vitaliano A; Lakwo, Thomson; Mekasha, Sindeaw; Abanyie, Francisca; Sleshi, Markos; Kebede, Amha; Cantey, Paul T

2016-04-01

Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N= 500 each) and "residual" skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(-) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools. © The American Society of Tropical Medicine and Hygiene.

Immune recognition of Onchocerca volvulus proteins in the human host and animal models of onchocerciasis.

PubMed

Manchang, T K; Ajonina-Ekoti, I; Ndjonka, D; Eisenbarth, A; Achukwi, M D; Renz, A; Brattig, N W; Liebau, E; Breloer, M

2015-05-01

Onchocerca volvulus is a tissue-dwelling, vector-borne nematode parasite of humans and is the causative agent of onchocerciasis or river blindness. Natural infections of BALB/c mice with Litomosoides sigmodontis and of cattle with Onchocerca ochengi were used as models to study the immune responses to O. volvulus-derived recombinant proteins (OvALT-2, OvNLT-1, Ov103 and Ov7). The humoral immune response of O. volvulus-infected humans against OvALT-2, OvNLT-1 and Ov7 revealed pronounced immunoglobulin G (IgG) titres which were, however, significantly lower than against the lysate of O. volvulus adult female worms. Sera derived from patients displaying the hyperreactive form of onchocerciasis showed a uniform trend of higher IgG reactivity both to the single proteins and the O. volvulus lysate. Sera derived from L. sigmodontis-infected mice and from calves exposed to O. ochengi transmission in a hyperendemic area also contained IgM and IgG1 specific for O. volvulus-derived recombinant proteins. These results strongly suggest that L. sigmodontis-specific and O. ochengi-specific immunoglobulins elicited during natural infection of mice and cattle cross-reacted with O. volvulus-derived recombinant antigens. Monitoring O. ochengi-infected calves over a 26-month period, provided a comprehensive kinetic of the humoral response to infection that was strictly correlated with parasite load and occurrence of microfilariae.

Elimination of Onchocerca volvulus Transmission in the Huehuetenango Focus of Guatemala

PubMed Central

Cruz-Ortiz, Nancy; Gonzalez, Rodrigo J.; Lindblade, Kim A.; Richards, Frank O.; Sauerbrey, Mauricio; Zea-Flores, Guillermo; Dominguez, Alfredo; Oliva, Orlando; Catú, Eduardo; Rizzo, Nidia

2012-01-01

In Latin America, onchocerciasis is targeted for elimination by 2012 through twice-yearly mass treatment of the eligible population with ivermectin. In Guatemala, two of the four historical endemic foci have demonstrated elimination of transmission, following World Health Organization guidelines. Using established guidelines ophthalmological, serological, and entomological evaluations were conducted in 2007-8 to determine the transmission status of onchocerciasis in the Huehuetenango focus. The prevalence of Onchocerca volvulus microfilariae in the anterior segment of the eye in 365 residents was 0% (95% confidence interval [CI] 0–0.8%), the prevalence of infection of O. volvulus in Simulium ochraceum among 8252 flies collected between November 2007 and April 2008 was 0% (95% CI 0–0.02%), and the prevalence of antibodies to a recombinant O. volvulus antigen in 3118 school age children was 0% (95% CI 0–0.1%). These results showed transmission interruption; thus, in 2009 mass treatment was halted and posttreatment surveillance began. To verify for potential recrudescence an entomological evaluation (from December 2010 to April 2011) was conducted during the 2nd and 3rd year of posttreatment surveillance. A total of 4587 S. ochraceum were collected, and the prevalence of infection of O. volvulus was 0% (95% CI 0–0.04%). Transmission of onchocerciasis in the Huehuetenango focus has been eliminated. PMID:22970346

Onchocerciasis

MedlinePlus

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Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment.

PubMed

Bourguinat, Catherine; Pion, Sébastien D S; Kamgno, Joseph; Gardon, Jacques; Duke, Brian O L; Boussinesq, Michel; Prichard, Roger K

2007-08-30

Onchocerca volvulus is the causative agent of onchocerciasis, or "river blindness". Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure. O. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 microg/kg or 800 microg/kg. Genotype frequencies were determined in beta-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between beta-tubulin genotype and female parasite fertility. We found a significant selection for beta-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the beta-tubulin "aa" homozygotes from 68.6% to 25.6%, while the "ab" heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the beta-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p = 0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly. The results indicate that ivermectin is causing genetic selection on O. volvulus. This genetic selection is associated with a lower reproductive rate in the female parasites. We hypothesize that this genetic selection indicates that a population of O. volvulus, which is more tolerant to ivermectin, is being selected. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes.

Onchocerciasis transmission in Ghana: the human blood index of sibling species of the Simulium damnosum complex.

PubMed

Lamberton, Poppy H L; Cheke, Robert A; Walker, Martin; Winskill, Peter; Crainey, J Lee; Boakye, Daniel A; Osei-Atweneboana, Mike Y; Tirados, Iñaki; Wilson, Michael D; Tetteh-Kumah, Anthony; Otoo, Sampson; Post, Rory J; Basañez, María-Gloria

2016-08-05

Vector-biting behaviour is important for vector-borne disease (VBD) epidemiology. The proportion of blood meals taken on humans (the human blood index, HBI), is a component of the biting rate per vector on humans in VBD transmission models. Humans are the definitive host of Onchocerca volvulus, but the simuliid vectors feed on a range of animals and HBI is a key indicator of the potential for human onchocerciasis transmission. Ghana has a diversity of Simulium damnosum complex members, which are likely to vary in their HBIs, an important consideration for parameterization of onchocerciasis control and elimination models. Host-seeking and ovipositing S. damnosum (sensu lato) (s.l.) were collected from seven villages in four Ghanaian regions. Taxa were morphologically and molecularly identified. Blood meals from individually stored blackfly abdomens were used for DNA profiling, to identify previous host choice. Household, domestic animal, wild mammal and bird surveys were performed to estimate the density and diversity of potential blood hosts of blackflies. A total of 11,107 abdomens of simuliid females (which would have obtained blood meal(s) previously) were tested, with blood meals successfully amplified in 3,772 (34 %). A single-host species was identified in 2,857 (75.7 %) of the blood meals, of which 2,162 (75.7 %) were human. Simulium soubrense Beffa form, S. squamosum C and S. sanctipauli Pra form were the most anthropophagic (HBI = 0.92, 0.86 and 0.70, respectively); S. squamosum E, S. yahense and S. damnosum (sensu stricto) (s.s.)/S. sirbanum were the most zoophagic (HBI = 0.44, 0.53 and 0.63, respectively). The degree of anthropophagy decreased (but not statistically significantly) with increasing ratio of non-human/human blood hosts. Vector to human ratios ranged from 139 to 1,198 blackflies/person. DNA profiling can successfully identify blood meals from host-seeking and ovipositing blackflies. Host choice varies according to sibling species, season and capture site/method. There was no evidence that HBI is vector and/or host density dependent. Transmission breakpoints will vary among locations due to differing cytospecies compositions and vector abundances.

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon.

PubMed

Kouam, Marc K; Tchatchueng-Mbougua, Jules B; Demanou, Maurice; Boussinesq, Michel; Pion, Sébastien D S; Kamgno, Joseph

2013-09-27

Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999-2000. There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999-2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is an indication that the risk of occurrence of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time.

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon

PubMed Central

2013-01-01

Background Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. Methods A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999–2000. Results There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999–2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. Conclusion The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is an indication that the risk of occurrence of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time. PMID:24289520

[Ivermectin as an adjunct in the treatment of refractory epilepsy].

PubMed

Diazgranados-Sanchez, J A; Mejia-Fernandez, J L; Chan-Guevara, L S; Valencia-Artunduaga, M H; Costa, J L

2017-10-01

Ivermectin, a 22'23 dihydro derivative of avermectins beta-1a, is a highly effective veterinary and human anti parasitic, used to treat endoparasites of difficult control such as filariasis and onchocerciasis, with a median plasma life of at least of 16 hours. The recommended therapeutic doses range from 0.05 to 0.40 mg/kg, without undesirable effects or risk to human life. It went from being a great success in animal health to its application in humans, where it has had great impact. Studies in basic sciences have shown that ivermectin has anticonvulsive effects in different epileptic animal models, where five different mechanisms of action have been described. Descriptive, prospective observational study, performed between 2013 and 2015, with 32 refractory epileptic patients, who received ivermectin as an a dose of adjunctive treatment of 10 mg/day three or seven times a week, controlled every three months, followed by 12-24 months, without withdrawal of anticonvulsant medications that they received previously. Progressively, patients entered into crisis control, at the end of the programmed follow-up period, the total percentage of crisis reduction was 97%, of which 57% did not return to crisis from the beginning of treatment, all patients being free of crisis according to International League Against Epilepsy criteria. Ivermectin has been useful as an adjuvant, achieving a significant decrease in seizures in this group of drug resistant patients.

Global epidemiology, ecology and control of soil-transmitted helminth infections

PubMed Central

Brooker, Simon; Clements, Archie CA; Bundy, Don AP

2007-01-01

Soil-transmitted helminth (STH) infections are among the most prevalent of chronic human infections worldwide. Based on the demonstrable impact on child development, there is a global commitment to finance and implement control strategies with a focus on school-based chemotherapy programmes. The major obstacle to the implementation of cost-effective control is the lack of accurate descriptions of the geographical distribution of infection. In recent years considerable progress has been made in the use of geographical information systems (GIS) and remote sensing (RS) to better understand helminth ecology and epidemiology, and to develop low cost ways to identify target populations for treatment. This chapter explores how this information has been used practically to guide large-scale control programmes. The use of satellite-derived environmental data has yielded new insights into the ecology of infection at a geographical scale that has proven impossible to address using more traditional approaches, and has in turn allowed spatial distributions of infection prevalence to be predicted robustly by statistical approaches. GIS/RS have increasingly been used in the context of large-scale helminth control programmes, including not only STH infections but also those focusing on schistosomiasis, filariasis and onchocerciasis. The experience indicates that GIS/RS provides a cost-effective approach to designing and monitoring programs at realistic scale. Importantly, the use of this approach has begun to transition from being a specialist approach of international vertical programs to become a routine tool in developing public sector control programs. GIS/RS is used here to describe the global distribution of STH infections and to estimate the number of infections in school age children in sub-Saharan Africa (89.9 million) and the annual cost of providing a single anthelmintic treatment using a school-based approach (US$5.0-7.6 million). These are the first estimates at a continental scale to explicitly include the fine spatial distribution of infection prevalence and population, and suggest that traditional methods have overestimated the situation. The results suggest that continent-wide control of parasites is, from a financial perspective, an attainable goal. PMID:16647972

[The Brazilian focus of onchocerciasis: new observations in the areas of the Mucajaí and Catrimâni rivers, Territory of Roraima].

PubMed

Moraes, M A; Shelley, A J; Luna Dias, A P

1986-01-01

A recent survey for onchocerciasis conducted among the Yanomami Indians living on the middle reaches of the Mucajaí and Catrimâni Rivers (Territory of Roraima) has failed to show any alteration in the local pattern of the disease. In fact, after a decade from the first surveys in these areas located at the periphery of the Yanomami focus, the prevalence and the intensity of infection have not experienced a significant change. Considering only the residents in the villages inside the surveyed areas, the prevalence varied from zero in the neighbourhood of the Catrimâni mission to 3.1 per cent near the Mucajaí mission. Had there been a competent vector of Onchocerca volvulus in the region higher rates might be expected due to the Yanomami custom of periodic visits among the groups of the tribe. In some of these visits, numbers of highly infected Indians from the central and mountainous part of the Yanomami territory--where more than 90 per cent of the adults have onchocerciasis--come to the villages in the lowland area, attracted by the facilities offered by the mission posts. As the visitors stay in the host villages for several days or weeks, the residents could become exposed to the disease. Simulium oyapockense s.1., a man-biting species of black fly, widely distributed in Northern Brazil, is the only possible vector of O. volvulus in the investigated areas, on the grounds of its local abundance.(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

PubMed Central

Bourguinat, Catherine; Pion, Sébastien D. S.; Kamgno, Joseph; Gardon, Jacques

2007-01-01

Background Onchocerca volvulus is the causative agent of onchocerciasis, or “river blindness”. Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure. Methods and Findings O. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 µg/kg or 800 µg/kg. Genotype frequencies were determined in β-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between β-tubulin genotype and female parasite fertility. We found a significant selection for β-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the β-tubulin “aa” homozygotes from 68.6% to 25.6%, while the “ab” heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the β-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p = 0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly. Conclusions The results indicate that ivermectin is causing genetic selection on O. volvulus. This genetic selection is associated with a lower reproductive rate in the female parasites. We hypothesize that this genetic selection indicates that a population of O. volvulus, which is more tolerant to ivermectin, is being selected. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes. PMID:17989786

Comparison of Doxycycline, Minocycline, Doxycycline plus Albendazole and Albendazole Alone in Their Efficacy against Onchocerciasis in a Randomized, Open-Label, Pilot Trial

PubMed Central

Batsa, Linda; Ayisi-Boateng, Nana Kwame; Osei-Mensah, Jubin; Mubarik, Yusif; Konadu, Peter; Ricchiuto, Arcangelo; Fimmers, Rolf; Arriens, Sandra; Dubben, Bettina; Ford, Louise; Taylor, Mark; Hoerauf, Achim

2017-01-01

The search for new macrofilaricidal drugs against onchocerciasis that can be administered in shorter regimens than required for doxycycline (DOX, 200mg/d given for 4–6 weeks), identified minocycline (MIN) with superior efficacy to DOX. Further reduction in the treatment regimen may be achieved with co-administration with standard anti-filarial drugs. Therefore a randomized, open-label, pilot trial was carried out in an area in Ghana endemic for onchocerciasis, comprising 5 different regimens: the standard regimen DOX 200mg/d for 4 weeks (DOX 4w, N = 33), the experimental regimens MIN 200mg/d for 3 weeks (MIN 3w; N = 30), DOX 200mg/d for 3 weeks plus albendazole (ALB) 800mg/d for 3 days (DOX 3w + ALB 3d, N = 32), DOX 200mg/d for 3 weeks (DOX 3w, N = 31) and ALB 800mg for 3 days (ALB 3d, N = 30). Out of 158 randomized participants, 116 (74.4%) were present for the follow-up at 6 months of whom 99 participants (63.5%) followed the treatment per protocol and underwent surgery. Histological analysis of the adult worms in the extirpated nodules revealed absence of Wolbachia in 98.8% (DOX 4w), 81.4% (DOX 3w + ALB 3d), 72.7% (MIN 3w), 64.1% (DOX 3w) and 35.2% (ALB 3d) of the female worms. All 4 treatment regimens showed superiority to ALB 3d (p < 0.001, p < 0.001, p = 0.002, p = 0.008, respectively), which was confirmed by real-time PCR. Additionally, DOX 4w showed superiority to all other treatment arms. Furthermore DOX 4w and DOX 3w + ALB 3d showed a higher amount of female worms with degenerated embryogenesis compared to ALB 3d (p = 0.028, p = 0.042, respectively). These results confirm earlier studies that DOX 4w is sufficient for Wolbachia depletion and the desired parasitological effects. The data further suggest that there is an additive effect of ALB (3 days) on top of that of DOX alone, and that MIN shows a trend for stronger potency than DOX. These latter two results are preliminary and need confirmation in a fully randomized controlled phase 2 trial. Trial Registration: ClinicalTrials.gov #06010453 PMID:28056021

Neglected tropical diseases in Brazil.

PubMed

Lindoso, José Angelo L; Lindoso, Ana Angélica B P

2009-01-01

Poverty is intrinsically related to the incidence of Neglected Tropical Diseases (NTDs). The main countries that have the lowest human development indices (HDI) and the highest burdens of NTDs are located in tropical and subtropical regions of the world. Among these countries is Brazil, which is ranked 70th in HDI. Nine out of the ten NTDs established by the World Health Organization (WHO) are present in Brazil. Leishmaniasis, tuberculosis, dengue fever and leprosy are present over almost the entire Brazilian territory. More than 90% of malaria cases occur in the Northern region of the country, and lymphatic filariasis and onchocerciasis occur in outbreaks in a particular region. The North and Northeast regions of Brazil have the lowest HDIs and the highest rates of NTDs. These diseases are considered neglected because there is not important investment in projects for the development of new drugs and vaccines and existing programs to control these diseases are not sufficient. Another problem related to NTDs is co-infection with HIV, which favors the occurrence of severe clinical manifestations and therapeutic failure. In this article, we describe the status of the main NTDs currently occurring in Brazil and relate them to the HDI and poverty.

The burden of neglected tropical diseases in Ethiopia, and opportunities for integrated control and elimination

PubMed Central

2012-01-01

Background Neglected tropical diseases (NTDs) are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward. Results This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA), the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway. Conclusion Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of NTDs, integrated mapping, rapid scale up of interventions and operational research into co implementation of intervention packages will be crucial. PMID:23095679

Productivity Loss Related to Neglected Tropical Diseases Eligible for Preventive Chemotherapy: A Systematic Literature Review

PubMed Central

Rijnsburger, Adriana J.; Severens, Johan L.

2016-01-01

Background Neglected Tropical Diseases (NTDs) not only cause health and life expectancy loss, but can also lead to economic consequences including reduced ability to work. This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five worldwide most prevalent NTDs: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (ascariasis, trichuriasis, and hookworm infection) and trachoma. These diseases are eligible to preventive chemotherapy (PCT). Methodology/Principal Findings Eleven bibliographic databases were searched using different names of all NTDs and various keywords relating to productivity. Additional references were identified through reference lists from relevant papers. Of the 5316 unique publications found in the database searches, thirteen papers were identified for lymphatic filariasis, ten for onchocerciasis, eleven for schistosomiasis, six for soil-transmitted helminths and three for trachoma. Besides the scarcity in publications reporting the degree of productivity loss, this review revealed large variation in the estimated productivity loss related to these NTDs. Conclusions It is clear that productivity is affected by NTDs, although the actual impact depends on the type and severity of the NTD as well as on the context where the disease occurs. The largest impact on productivity loss of individuals affected by one of these diseases seems to be due to blindness from onchocerciasis and severe schistosomiasis manifestations; productivity loss due to trachoma-related blindness has never been studied directly. However, productivity loss at an individual level might differ from productivity loss at a population level because of differences in the prevalence of NTDs. Variation in estimated productivity loss between and within diseases is caused by differences in research methods and setting. Publications should provide enough information to enable readers to assess the quality and relevance of the study for their purposes. PMID:26890487

Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian focus.

PubMed

Botto, Carlos; Basañez, María-Gloria; Escalona, Marisela; Villamizar, Néstor J; Noya-Alarcón, Oscar; Cortez, José; Vivas-Martínez, Sarai; Coronel, Pablo; Frontado, Hortencia; Flores, Jorge; Graterol, Beatriz; Camacho, Oneida; Tovar, Yseliam; Borges, Daniel; Morales, Alba Lucia; Ríos, Dalila; Guerra, Francisco; Margeli, Héctor; Rodriguez, Mario Alberto; Unnasch, Thomas R; Grillet, María Eugenia

2016-01-27

The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. From 2010 to 2012-2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012-2013 were, respectively, under 1% and 20 L3/person/transmission season. Serology in children aged 1-10 years demonstrated that although 26 out of 396 (7%) individuals still had Ov-16 antibodies, only 4/218 (2%) seropositives were aged 1-5 years. We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75% of the Yanomami population and 70% of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus.

The Applications of Model-Based Geostatistics in Helminth Epidemiology and Control

PubMed Central

Magalhães, Ricardo J. Soares; Clements, Archie C.A.; Patil, Anand P.; Gething, Peter W.; Brooker, Simon

2011-01-01

Funding agencies are dedicating substantial resources to tackle helminth infections. Reliable maps of the distribution of helminth infection can assist these efforts by targeting control resources to areas of greatest need. The ability to define the distribution of infection at regional, national and subnational levels has been enhanced greatly by the increased availability of good quality survey data and the use of model-based geostatistics (MBG), enabling spatial prediction in unsampled locations. A major advantage of MBG risk mapping approaches is that they provide a flexible statistical platform for handling and representing different sources of uncertainty, providing plausible and robust information on the spatial distribution of infections to inform the design and implementation of control programmes. Focussing on schistosomiasis and soil-transmitted helminthiasis, with additional examples for lymphatic filariasis and onchocerciasis, we review the progress made to date with the application of MBG tools in large-scale, real-world control programmes and propose a general framework for their application to inform integrative spatial planning of helminth disease control programmes. PMID:21295680

Interruption of Onchocerca volvulus Transmission in the Abu Hamed Focus, Sudan

PubMed Central

Higazi, Tarig B.; Zarroug, Isam M. A.; Mohamed, Hanan A.; ElMubark, Wigdan A.; Deran, Tong Chor M.; Aziz, Nabil; Katabarwa, Moses; Hassan, Hassan K.; Unnasch, Thomas R.; Mackenzie, Charles D.; Richards, Frank; Hashim, Kamal

2013-01-01

Abu Hamed, Sudan, the northernmost location of onchocerciasis in the world, began community-directed treatment with ivermectin (CDTI) in 1998, with annual treatments enhanced to semiannual in 2007. We assessed the status of the parasite transmission in 2011 entomologically, parasitologically, and serologically. O-150 pool screening showed no parasite DNA in 17,537 black flies collected in 2011 (95% confidence interval upper limit [95% CI UL] = 0.023). Skin microfilariae, nodules, and signs of skin disease were absent in 536 individuals in seven local communities. Similarly, no evidence of Onchocerca volvulus Ov16 antibodies was found in 6,756 school children ≤ 10 years (95% CI UL = 0.03%). Because this assessment of the focus meets the 2001 World Health Organization (WHO) criteria for interrupted transmission, treatment was halted in 2012, and a post-treatment surveillance period was initiated in anticipation of declaration of disease elimination in this area. We provide the first evidence in East Africa that long-term CDTI alone can interrupt transmission of onchocerciasis. PMID:23690554

Polymerase Chain Reaction Pool Screening Used To Compare Prevalence of Infective Black Flies in Two Onchocerciasis Foci in Northern Sudan

PubMed Central

Higazi, Tarig B.; Zarroug, Isam M. A.; Mohamed, Hanan A.; Mohamed, Wigdan A.; Deran, Tong Chor M.; Aziz, Nabil; Katabarwa, Moses; Hassan, Hassan K.; Unnasch, Thomas R.; Mackenzie, Charles D.; Richards, Frank

2011-01-01

Onchocerciasis remains an important debilitating disease in many areas of Africa, including Sudan. The status of infection transmission in 2007 was assessed in the vectors of two disease foci in Sudan: Abu Hamed in northern Sudan, which has received at least 10 years of annual treatment and Galabat focus in eastern Sudan, where only minor, largely undocumented treatment activity has occurred. Assessment of more than 30,000 black flies for Onchocerca volvulus infectious stage L3 larvae by using an O-150 polymerase chain reaction protocol showed that black fly infectivity rates were 0.84 (95% confidence interval = 0.0497–1.88) per 10,000 flies for Abu Hamed and 6.9 (95% confidence interval = 1.1–16.4) infective flies per 10,000 for Galabat. These results provide entomologic evidence for suppressed Onchocerca volvulus transmission in the Abu Hamed focus and a moderate transmission rate of the parasite in the Galabat focus. PMID:21540385

Onchocerciasis control in Nigeria: will households be able to afford community-directed treatment with ivermectin?

PubMed

Onwujekwe, O; Shu, E; Onwuameze, O; Ndum, C; Okonkwo, P

2001-12-21

To determine the level of affordability of community-directed treatment with ivermectin (CDTI) to households living in two onchocerciasis endemic Nigerian communities namely Toro in the north and Nike in the south. The proportion of the cost of treating people with ivermectin will deplete in average monthly/projected annual household expenditure on food and health care, and on average monthly and projected annual household income were respectively calculated and used to determine the level of affordability of CDTI. Questionnaires administered to heads of households or their representatives were used to collect information on the household expenditures and income. The suggested unit CDTI cost of $0.20 was used. However, as a test of sensitivity, we also used the unit cost of $0.056 which some community based distributors are charging per treatment. Using $0.20 as the unit treatment cost, this will consume less than 0.05% of average annual household income in both communities. It will equally deplete 0.05% of combined annual household expenditures on food and health care in both communities. However, using $0.056 as the unit treatment cost, then 0.02% of average annual household expenditure on health care, 0.01% average annual expenditure on combined health care and food, and 0.01% of average annual household income will be depleted. The households living in both communities may be able to afford CDTI schemes. However, the final decision on levels of affordability lies with the households. They will decide whether they can afford to trade-off some household income for ivermectin distribution.

Integration of mass drug administration programmes in Nigeria: The challenge of schistosomiasis.

PubMed Central

Richards, Frank O.; Eigege, Abel; Miri, Emmanuel S.; Jinadu, M. Y.; Hopkins, Donald R.

2006-01-01

PROBLEM: Annual mass drug administration (MDA) with safe oral anthelminthic drugs (praziquantel, ivermectin and albendazole) is the strategy for control of onchocerciasis, lymphatic filariasis (LF) and schistosomiasis. District health officers seek to integrate treatment activities in areas of overlapping disease endemicity, but they are faced with having to merge different programmatic guidelines. APPROACH: We proceeded through the three stages of integrated MDA implementation: mapping the distribution of the three diseases at district level; tailoring district training and logistics based on the results of the mapping exercises; and implementing community-based annual health education and mass treatment where appropriate. During the process we identified the "know-do" gaps in the MDA guidelines for each disease that prevented successful integration of these programmes. LOCAL SETTING: An integrated programme launched in 1999 in Plateau and Nasarawa States in central Nigeria, where all three diseases were known to occur. RELEVANT CHANGES: Current guidelines allowed onchocerciasis and LF activities to be integrated, resulting in rapid mapping throughout the two states, and states-wide provision of over 9.3 million combined ivermectin-albendazole treatments for the two diseases between 2000 and 2004. In contrast, schistosomiasis activities could not be effectively integrated because of the more restrictive guidelines, resulting in less than half of the two states being mapped, and delivery of only 701,419 praziquantel treatments for schistosomiasis since 1999. LESSONS LEARNED: Integration of schistosomiasis into other MDA programmes would be helped by amended guidelines leading to simpler mapping, more liberal use of praziquantel and the ability to administer praziquantel simultaneously with ivermectin and albendazole. PMID:16917658

Still mesoendemic onchocerciasis in two Cameroonian community-directed treatment with ivermectin projects despite more than 15 years of mass treatment.

PubMed

Kamga, Guy-Roger; Dissak-Delon, Fanny N; Nana-Djeunga, Hugues C; Biholong, Benjamin D; Mbigha-Ghogomu, Stephen; Souopgui, Jacob; Zoure, Honorat G M; Boussinesq, Michel; Kamgno, Joseph; Robert, Annie

2016-11-14

After more than a decade of community-directed treatment with ivermectin (CDTI) in Centre and Littoral Regions of Cameroon, onchocerciasis endemicity was still high in some communities according to the 2011 epidemiological evaluations. Some corrective measures were undertaken to improve the CDTI process and therefore reduce the burden of the disease. The objective of the present study was to assess the progress made towards the elimination of onchocerciasis in the Centre 1 and Littoral 2 CDTI projects where the worst performances were found in 2011. To this end, a cross-sectional survey was conducted in April 2015 in eight communities in two health districts (HD), Bafia in Centre 1 and Yabassi in Littoral 2, chosen because assessed at baseline and in 2011. All volunteers living for at least five years in the community, aged five years or more, underwent clinical and parasitological examinations. Individual compliance to ivermectin treatment was also assessed. Analyses of data were weighted proportionally to age and gender distribution in the population. In the Bafia and Yabassi HD, 514 and 242 individuals were examined with a mean age of 35.1 (standard deviation, SD: 20.7) and 44.6 (SD: 16.3) years, respectively. In the Bafia HD, the weighted prevalences varied from 24.4 to 57.0 % for microfilaridermia and from 3.6 to 37.4 % for nodule presence across the surveyed communities. The community microfilarial load (CMFL), expressed in microfilariae/skin snip (mf/ss), significantly dropped from 20.84-114.50 mf/ss in 1991 to 0.31-1.62 mf/ss in 2015 in all the surveyed communities. In the Yabassi HD, the weighted prevalences varied from 12.3 to 59.3 % for microfilaridermia and from 1.5 to 3.7 % for nodule presence across the surveyed communities, while a significant drop was observed in CMFL, from 20.40-28.50 mf/ss in 1999 to 0.48-1.74 mf/ss in 2015. The 2014 weighted therapeutic coverage of participants varied from 65.8 % (95 % CI: 58.4-73.2) in Yabassi HD, to 68.0 % (95 % CI: 63.3-72.7) in Bafia HD, with important variations among communities. After more than 15 years of CDTI, onchocerciasis is still mesoendemic in the surveyed communities. Further studies targeting therapeutic coverage, socio-anthropological considerations of CDTI implementation and entomological studies would bring more insights to the persistence of the disease as observed in the present study.

A Controlled Trial to Assess the Effect of Quinine, Chloroquine, Amodiaquine, and Artesunate on Loa loa Microfilaremia

PubMed Central

Kamgno, Joseph; Djomo, Patrick Nguipdop; Pion, Sébastien D.; Thylefors, Björn; Boussinesq, Michel

2010-01-01

Onchocerciasis control is currently based on mass ivermectin treatment. Unfortunately, this drug can induce serious adverse events (SAEs) in persons with high levels of Loa loa microfilaremia (> 30,000 microfilaria/mL). A means of preventing SAEs would be to treat at risk populations with a drug that would progressively reduce the microfilarial loads before administering ivermectin. Antimalarial drugs are a potential solution because they have shown some activity against various filarial species. A controlled trial was conducted to assess the effect of standard doses of quinine, chloroquine, amodiaquine, and artesunate on L. loa microfilaremia. Ninety-eight patients were randomly allocated into five groups (one for each drug and a control group) after stratification on microfilarial load. Loa loa microfilaremia was monitored on days 0, 3, 7, 15, 30, 60, and 90. No significant change in the loads was recorded in any of the treatment groups. A comprehensive review of the effects of antimalarial drugs against filariae is also provided. PMID:20207860

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial.

PubMed

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C

2016-03-01

Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤ 30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥ 4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial

PubMed Central

Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C.

2016-01-01

Background Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Methodology Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. Principal Findings None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively. Conclusions/ Significance The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas. PMID:26967331

Pre-control relationship of onchocercal skin disease with onchocercal infection in Guinea Savanna, Northern Nigeria

PubMed Central

Murdoch, Michele E.; Murdoch, Ian E.; Evans, Jennifer; Yahaya, Haliru; Njepuome, Ngozi; Cousens, Simon; Abiose, Adenike

2017-01-01

Background Onchocerca volvulus infection can result in blindness, itching and skin lesions. Previous research concentrated on blindness. Methods A clinical classification system of the cutaneous changes in onchocerciasis was used for the first time in this study within the context of an early ivermectin drug trial in the savanna region of Kaduna State, northern Nigeria. Skin examinations were performed in 6,790 individuals aged 5+ years in endemic communities and 1,343 individuals in nonendemic communities. Results / Discussion There was increased risk for all forms of onchocercal skin disease in endemic communities with the most common finding being the presence of nodules (1,438 individuals, 21.2%), followed by atrophy (367, 6.1% of those < 50 years), acute papular onchodermatitis, APOD (233, 3.4%), depigmentation (216, 3.2%) and chronic papular onchodermatitis, CPOD (155, 2.3%). A further 645 individuals (9.5%) complained of pruritus but had completely normal skin. APOD was more common in males whereas atrophy, hanging groin and nodules were more common in females. After controlling for age and sex, microfilarial positivity was a risk factor for CPOD, depigmentation, hanging groin and nodules (OR 1.54, p = 0.046; OR 2.29, p = 0.002; OR 2.18, p = 0.002 and OR 3.80, p <0.001 respectively). Comparable results were found using presence of nodules as the marker for infection. Microfilarial load showed similar, though weaker, results. A total of 2621(38.6%) endemic residents had itching with normal skin, or had one or more types of onchocercal skin disease including nodules, which may be considered as a composite index of the overall prevalence of onchocercal skin disease. Conclusion Significant levels of onchocercal skin disease were documented in this savanna area, which subsequently resulted in a reassessment of the true burden of skin disease in onchocerciasis. This paper represents the first detailed report of the association of onchocercal skin disease with markers for onchocercal infection. PMID:28355223

A simple technique for maintaining Stimulium adults, including onchocerciasis vectors, under artificial conditions.

PubMed

Raybould, J N; Mhiddin, H K

1974-01-01

The maintenance of Simulium adults in the laboratory is necessary for many experimental investigations and is a prerequisite to laboratory colonization. A simple technique for this purpose is described in which each fly is kept separately in a hole bored in a block of expanded polystyrene.

Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors

PubMed Central

2010-01-01

Background In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. Methods In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. Results Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. Conclusions Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages. PMID:21171970

How do the macrocyclic lactones kill filarial nematode larvae?

PubMed

Wolstenholme, Adrian J; Maclean, Mary J; Coates, Ruby; McCoy, Ciaran J; Reaves, Barbara J

2016-09-01

The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system.

Immunization with L. sigmodontis Microfilariae Reduces Peripheral Microfilaraemia after Challenge Infection by Inhibition of Filarial Embryogenesis

PubMed Central

Ziewer, Sebastian; Hübner, Marc P.; Dubben, Bettina; Hoffmann, Wolfgang H.; Bain, Odile; Martin, Coralie; Hoerauf, Achim; Specht, Sabine

2012-01-01

Background Lymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems. Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation into infective stage to a new host. After closure of vector control programs, disease control relies mainly on mass drug administration with drugs that are primarily effective against first stage larvae and require many years of annual/biannual administration. Therefore, there is an urgent need for alternative treatment ways, i.e. other effective drugs or vaccines. Methodology/Principal Findings Using the Litomosoides sigmodontis murine model of filariasis we demonstrate that immunization with microfilariae together with the adjuvant alum prevents mice from developing high microfilaraemia after challenge infection. Immunization achieved 70% to 100% protection in the peripheral blood and in the pleural space and furthermore strongly reduced the microfilarial load in mice that remained microfilaraemic. Protection was associated with the impairment of intrauterine filarial embryogenesis and with local and systemic microfilarial-specific host IgG, as well as IFN-γ secretion by host cells from the site of infection. Furthermore immunization significantly reduced adult worm burden. Conclusions/Significance Our results present a tool to understand the immunological basis of vaccine induced protection in order to develop a microfilariae-based vaccine that reduces adult worm burden and prevents microfilaraemia, a powerful weapon to stop transmission of filariasis. PMID:22413031

Preventive chemotherapy in human helminthiasis: theoretical and operational aspects

PubMed Central

Chitsulo, L.; Engels, D.; Savioli, L.

2017-01-01

Preventive chemotherapy (PC), the large-scale distribution of anthelminthic drugs to population groups at risk, is the core intervention recommended by the WHO for reducing morbidity and transmission of the four main helminth infections, namely lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis. The strategy is widely implemented worldwide but its general theoretical foundations have not been described so far in a comprehensive and cohesive manner. Starting from the information available on the biological and epidemiological characteristics of helminth infections, as well as from the experience generated by disease control and elimination interventions across the world, we extrapolate the fundamentals and synthesise the principles that regulate PC and justify its implementation as a sound and essential public health intervention. The outline of the theoretical aspects of PC contributes to a thorough understanding of the different facets of this strategy and helps comprehend opportunities and limits of control and elimination interventions directed against helminth infections. PMID:22040463

Transmission of Onchocerca volvulus Continues in Nyagak-Bondo Focus of Northwestern Uganda after 18 Years of a Single Dose of Annual Treatment with Ivermectin

PubMed Central

Katabarwa, Moses N.; Lakwo, Tom; Habomugisha, Peace; Agunyo, Stella; Byamukama, Edson; Oguttu, David; Tukesiga, Ephraim; Unoba, Dickson; Dramuke, Patrick; Onapa, Ambrose; Tukahebwa, Edridah M.; Lwamafa, Dennis; Walsh, Frank; Unnasch, Thomas R.

2013-01-01

The objective of the study was to determine whether annual ivermectin treatment in the Nyagak-Bondo onchocerciasis focus could safely be withdrawn. Baseline skin snip microfilariae (mf) and nodule prevalence data from six communities were compared with data collected in the 2011 follow-up in seven communities. Follow-up mf data in 607 adults and 145 children were compared with baseline (300 adults and 58 children). Flies collected in 2011were dissected, and poolscreen analysis was applied to ascertain transmission. Nodule prevalence in adults dropped from 81.7% to 11.0% (P < 0.0001), and mf prevalence dropped from 97.0% to 23.2% (P < 0.0001). In children, mf prevalence decreased from 79.3% to 14.1% (P < 0.0001). Parous and infection rates of 401 flies that were dissected were 52.9% and 1.5%, respectively, whereas the infective rate on flies examination by polymerase chain reaction (PCR) was 1.92% and annual transmission potential was 26.9. Stopping ivermectin treatment may result in onchocerciasis recrudescence. PMID:23690555

The prevalence, intensity and clinical manifestations of Onchocerca volvulus infection in Toro local government area of Bauchi State, Nigeria.

PubMed

Anosike, J C; Celestine; Onwuliri, O E; Onwuliri, V A

2001-07-01

Between January and October 1994, a study of the prevalence, intensity and clinical manifestations of onchocerciasis in nine communities of Toro local government area of Bauchi State, Nigeria was undertaken using the skin-snip method. Of the 1117 inhabitants examined, 188 (16.8%) were positive for microfilariae of Onchocerca volvulus. The prevalence of onchocerciasis was significantly higher (P < 0.05) among males than females, in subjects 21 years of age and above than in those in the first two decades of life, in nomads, farmers, hunters and fishermen than smiths and traders. Intensity of infection was light, not exceeding a geometric mean of 5.3 microfilaria per 2 mm skin bite. Preponderance of positive cases below 20 years presented no chronic signs. Conversely, persons above 20 years had higher microfilaria counts which coincides with the period when most clinical signs manifest. Microfilarial-rate and -density in relation to age were closely associated (r = 0.75, P < 0.001). The need for a sustained mass distribution of Mectizan in these communities is highlighted.

The applications of model-based geostatistics in helminth epidemiology and control.

PubMed

Magalhães, Ricardo J Soares; Clements, Archie C A; Patil, Anand P; Gething, Peter W; Brooker, Simon

2011-01-01

Funding agencies are dedicating substantial resources to tackle helminth infections. Reliable maps of the distribution of helminth infection can assist these efforts by targeting control resources to areas of greatest need. The ability to define the distribution of infection at regional, national and subnational levels has been enhanced greatly by the increased availability of good quality survey data and the use of model-based geostatistics (MBG), enabling spatial prediction in unsampled locations. A major advantage of MBG risk mapping approaches is that they provide a flexible statistical platform for handling and representing different sources of uncertainty, providing plausible and robust information on the spatial distribution of infections to inform the design and implementation of control programmes. Focussing on schistosomiasis and soil-transmitted helminthiasis, with additional examples for lymphatic filariasis and onchocerciasis, we review the progress made to date with the application of MBG tools in large-scale, real-world control programmes and propose a general framework for their application to inform integrative spatial planning of helminth disease control programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Amazonian onchocerciasis: parasitological profiles by host-age, sex, and endemicity in southern Venezuela.

PubMed

Vivas-Martínez, S; Basáñez, M G; Botto, C; Rojas, S; García, M; Pacheco, M; Curtis, C F

2000-11-01

This paper describes, for the human onchocerciasis focus of southern Venezuela, the age profiles of Onchocerca volvulus microfilarial (mf) and nodule prevalence, mf intensity, and mf aggregation for the whole examined population (836 Yanomami people) living in 20 villages, and for these communities classified according to endemicity levels (hypoendemic: < or = 20 %; mesoendemic: 21-59 %; hyperendemic: < or = 60 % infected). Mf prevalence and intensity increased with age, particularly in the hyperendemic areas, and there were no marked differences between the sexes. The prevalence of nodules followed the same age pattern. Fifty percent mf prevalence was reached in the 15-19 year age-class when the population was taken as a whole; nearly in the 10 to 14-year-olds for the hyperendemic level, in those aged 20-29 years in mesoendemic areas, and not reached at all in hypoendemic villages. The degree of mf aggregation was measured by the k value of the negative binomial distribution and by the variance to mean ratio (VMR). The relationship between the standard deviation (S.D.) of mf counts and the mean mf density was also explored. These 3 indices (k, VMR, and S.D.) showed a tendency to increase with both mean mf load and host age. Since infection intensity and host age were themselves positively related, it was not possible to draw definite conclusions about age-specific changes of parasite aggregation. There was not a significant decrease of mf intensity after an earlier peak neither was there a shift towards younger ages of the maximum no. of mf/mg reached as the endemicity level increased. These results are discussed in relation to detection of density dependence in the human host, selection of an indicator age-group for rapid epidemiological assessment (REA) methods, and strategies of ivermectin distribution in the Amazonian focus. It is recommended that, for the Amazonian onchocerciasis focus, the indicator group for REA consists of all those aged 15 years and over.

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

PubMed

Hess, Jessica A; Zhan, Bin; Torigian, April R; Patton, John B; Petrovsky, Nikolai; Zhan, Tingting; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David

2016-07-01

In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.

A simple technique for maintaining Simulium adults, including onchocerciasis vectors, under artificial conditions*

PubMed Central

Raybould, John N.; Mhiddin, Haji K.

1974-01-01

The maintenance of Simulium adults in the laboratory is necessary for many experimental investigations and is a prerequisite to laboratory colonization. A simple technique for this purpose is described in which each fly is kept separately in a hole bored in a block of expanded polystyrene. ImagesFig. 1 PMID:4549353

[Diagnosis and evolution of scabies].

PubMed

Piérard-Franchimont, C; Hermanns-Lê, T; Piérard, G E

2014-01-01

Human scabies is an ectoparasitosis affecting any individual at any age. The level of infestation by Sarcoptes scabiei var. hominis is influenced by any defect in immune response. Several clinical types of scabies are described including baby scabies, profuse scabies of immunodepression, norvegian scabies and sarcoptic mange. Onchocerciasis dermatitis is a tropical microfilariosis completely distinct by its parasitic nature.

Rapid mapping of schistosomiasis and other neglected tropical diseases in the context of integrated control programmes in Africa

PubMed Central

BROOKER, S.; KABATEREINE, N. B.; GYAPONG, J. O.; STOTHARD, J. R.; UTZINGER, J.

2009-01-01

SUMMARY There is growing interest and commitment to the control of schistosomiasis and other so-called neglected tropical diseases (NTDs). Resources for control are inevitably limited, necessitating assessment methods that can rapidly and accurately identify and map high-risk communities so that interventions can be targeted in a spatially-explicit and cost-effective manner. Here, we review progress made with (i) mapping schistosomiasis across Africa using available epidemiological data and more recently, climate-based risk prediction; (ii) the development and use of morbidity questionnaires for rapid identification of high-risk communities of urinary schistosomiasis; and (iii) innovative sampling-based approaches for intestinal schistosomiasis, using the lot quality assurance sampling technique. Experiences are also presented for the rapid mapping of other NTDs, including onchocerciasis, loiasis and lymphatic filariasis. Future directions for an integrated rapid mapping approach targeting multiple NTDs simultaneously are outlined, including potential challenges in developing an integrated survey tool. The lessons from the mapping of human helminth infections may also be relevant for the rapid mapping of malaria as its control efforts are intensified. PMID:19450373

Impact of Long-Term Treatment with Ivermectin on the Prevalence and Intensity of Soil-Transmitted Helminth Infections

PubMed Central

Moncayo, Ana Lucia; Vaca, Maritza; Amorim, Leila; Rodriguez, Alejandro; Erazo, Silvia; Oviedo, Gisela; Quinzo, Isabel; Padilla, Margarita; Chico, Martha; Lovato, Raquel; Gomez, Eduardo; Barreto, Mauricio L.; Cooper, Philip J.

2008-01-01

Background Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children. Methods and Findings A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6–16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0–5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR =  0.06, 95% CI 0.03–0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11–0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments. Conclusion Annual and twice-annual treatments with ivermectin over a period of up to 17 years may have had a significant impact on T. trichiura infection. The present data indicate that the long-term control of onchocerciasis with ivermectin may provide additional health benefits by reducing infections with trichuriasis. The addition of a second anthelmintic drug such as albendazole may be useful for a long-term effect on A. lumbricoides infection. PMID:18820741

Community financing of local ivermectin distribution in Nigeria: potential payment and cost-recovery outlook.

PubMed

Onwujekwe, O E; Shu, E N; Okonkwo, P O

2000-04-01

The preferred payment mechanism in a community financing scheme for local ivermectin distribution was elicited from randomly selected household heads from three communities in Nigeria using interviewer-administered structured questionnaires. The majority of the respondents in the three communities were prepared to pay for local ivermectin distribution. Additionally, the average amounts the respondents were prepared to pay per person treated ($0.28, $0.30 and $0.38 in Nike, Achi and Toro, respectively) were all more than the $0.20 ceiling recommended by the partners of the African Programme on Onchocerciasis Control (APOC). Thus, the cost-recovery outlook is bright in these communities. However, the preferred payment modality varied. Fee-for-service was the predominant payment modality in the Achi and Nike communities, while the Toro community preferred pre-payment. This study demonstrates that many communities have different payment preferences for endemic disease control efforts. This knowledge will help in developing acceptable and sustainable schemes. The imposition of unacceptable payment mechanisms will lead to an unwillingness to pay.

Analysis of the mdr-1 Gene in Patients Co-Infected with Onchocerca volvulus and Loa loa Who Experienced a Post-Ivermectin Serious Adverse Event

PubMed Central

Bourguinat, Catherine; Kamgno, Joseph; Boussinesq, Michel; Mackenzie, Charles D.; Prichard, Roger K.; Geary, Timothy G.

2010-01-01

Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Loa loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Loa mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs. PMID:20595473

Preventive chemotherapy in human helminthiasis: theoretical and operational aspects.

PubMed

Gabrielli, A-F; Montresor, A; Chitsulo, L; Engels, D; Savioli, L

2011-12-01

Preventive chemotherapy (PC), the large-scale distribution of anthelminthic drugs to population groups at risk, is the core intervention recommended by the WHO for reducing morbidity and transmission of the four main helminth infections, namely lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis. The strategy is widely implemented worldwide but its general theoretical foundations have not been described so far in a comprehensive and cohesive manner. Starting from the information available on the biological and epidemiological characteristics of helminth infections, as well as from the experience generated by disease control and elimination interventions across the world, we extrapolate the fundamentals and synthesise the principles that regulate PC and justify its implementation as a sound and essential public health intervention. The outline of the theoretical aspects of PC contributes to a thorough understanding of the different facets of this strategy and helps comprehend opportunities and limits of control and elimination interventions directed against helminth infections. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Review of the factors influencing the motivation of community drug distributors towards the control and elimination of neglected tropical diseases (NTDs)

PubMed Central

Gyapong, Margaret; Mallya, Shruti; Boadu, Nana Yaa; Amuyunzu-Nyamongo, Mary; Stephens, Mariana; McFarland, Deborah A.

2017-01-01

Background Community drug distributors or neglected tropical disease (NTD) volunteers have played a crucial role in ensuring the success of mass drug administration (MDA) programs using preventive chemotherapy (PC) for lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminths. In recent years however, a noticeable decline in motivation of some of these volunteers has been perceived, potentially negatively impacting the success of these programs. Potential hypotheses for this change in motivation include the long duration of many MDA programs, the change in sociocultural environments as well as the changes to the programs over time. This literature review identifies factors that affect NTD volunteer performance and motivation, which may be used to influence and improve future programming. Methodology/Principal findings A systematic search was conducted to identify studies published between January 1995 and September 2016 that investigate factors pertaining to volunteer motivation and performance in NTD drug distribution programs. Searches from several databases and grey literature yielded 400 records, of which 28 articles from 10 countries met the inclusion criteria. Quality assessment of studies was performed using the Critical Appraisal Skills Programme(CASP) checklist. Data pertaining to motivation, performance, retention and satisfaction was extracted and examined for themes. Recurring themes in the literature included monetary and material incentives, intrinsic motivation, gender, cost to participate, and health systems and community support. Of these, community support and the health system were found to be particularly impactful. Very few studies were found to explicitly look at novel incentives for volunteers and very few studies have considered the out of pocket and opportunity costs that NTD volunteers bear carrying out their tasks. Conclusions/Significance There is currently great interest in incorporating more attractive incentive schemes for NTD volunteers. However, our results show that the important challenges that volunteers face (cultural, health systems, financial and community related) may have less to do with financial incentives and may actually have a larger impact on their motivation than has previously been understood. Further integration of NTD programs into existing health systems is expected to improve the NTD volunteer working environment. Relevant community engagement related to the MDA program should also provide the supportive environment needed in the community to support NTD volunteers. Programs need to consider these issues to improve working conditions for NTD volunteers. PMID:29211746

Review of the factors influencing the motivation of community drug distributors towards the control and elimination of neglected tropical diseases (NTDs).

PubMed

Krentel, Alison; Gyapong, Margaret; Mallya, Shruti; Boadu, Nana Yaa; Amuyunzu-Nyamongo, Mary; Stephens, Mariana; McFarland, Deborah A

2017-12-01

Community drug distributors or neglected tropical disease (NTD) volunteers have played a crucial role in ensuring the success of mass drug administration (MDA) programs using preventive chemotherapy (PC) for lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminths. In recent years however, a noticeable decline in motivation of some of these volunteers has been perceived, potentially negatively impacting the success of these programs. Potential hypotheses for this change in motivation include the long duration of many MDA programs, the change in sociocultural environments as well as the changes to the programs over time. This literature review identifies factors that affect NTD volunteer performance and motivation, which may be used to influence and improve future programming. A systematic search was conducted to identify studies published between January 1995 and September 2016 that investigate factors pertaining to volunteer motivation and performance in NTD drug distribution programs. Searches from several databases and grey literature yielded 400 records, of which 28 articles from 10 countries met the inclusion criteria. Quality assessment of studies was performed using the Critical Appraisal Skills Programme(CASP) checklist. Data pertaining to motivation, performance, retention and satisfaction was extracted and examined for themes. Recurring themes in the literature included monetary and material incentives, intrinsic motivation, gender, cost to participate, and health systems and community support. Of these, community support and the health system were found to be particularly impactful. Very few studies were found to explicitly look at novel incentives for volunteers and very few studies have considered the out of pocket and opportunity costs that NTD volunteers bear carrying out their tasks. There is currently great interest in incorporating more attractive incentive schemes for NTD volunteers. However, our results show that the important challenges that volunteers face (cultural, health systems, financial and community related) may have less to do with financial incentives and may actually have a larger impact on their motivation than has previously been understood. Further integration of NTD programs into existing health systems is expected to improve the NTD volunteer working environment. Relevant community engagement related to the MDA program should also provide the supportive environment needed in the community to support NTD volunteers. Programs need to consider these issues to improve working conditions for NTD volunteers.

Vectorborne diseases in West Africa: geographic distribution and geospatial characteristics.

PubMed

Ratmanov, Pavel; Mediannikov, Oleg; Raoult, Didier

2013-05-01

This paper provides an overview of the methods in which geographic information systems (GIS) and remote sensing (RS) technology have been used to visualise and analyse data related to vectorborne diseases (VBD) in West Africa and to discuss the potential for these approaches to be routinely included in future studies of VBDs. GIS/RS studies of diseases that are associated with a specific geographic landscape were reviewed, including malaria, human African trypanosomiasis, leishmaniasis, lymphatic filariasis, Loa loa filariasis, onchocerciasis, Rift Valley fever, dengue, yellow fever, borreliosis, rickettsioses, Buruli ulcer and Q fever. RS data and powerful spatial modelling methods improve our understanding of how environmental factors affect the vectors and transmission of VBDs. There is great potential for the use of GIS/RS technologies in the surveillance, prevention and control of vectorborne and other infectious diseases in West Africa.

The Population Biology and Transmission Dynamics of Loa loa.

PubMed

Whittaker, Charles; Walker, Martin; Pion, Sébastien D S; Chesnais, Cédric B; Boussinesq, Michel; Basáñez, María-Gloria

2018-04-01

Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Filaricidal activities on Onchocerca ochengi and Loa loa, toxicity and phytochemical screening of extracts of Tragia benthami and Piper umbellatum.

PubMed

Cho-Ngwa, Fidelis; Monya, Elvis; Azantsa, Boris K; Manfo, Faustin Pascal T; Babiaka, Smith B; Mbah, James A; Samje, Moses

2016-08-30

Onchocerciasis is the world's second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L. loa microfilariae (mf). Fourteen extracts from two medicinal plants, Tragia benthami and Piper umbellatum were screened in vitro against Onchocerca ochengi parasite and L. loa mf. Activities of extracts on male worms and microfilariae were assessed by motility reduction, while MTT/Formazan assay was used to assess biochemically the death of female worms. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney cells and Balb/c mice, respectively. At 500 μg/mL, all extracts showed 100 % activity on Onchocerca ochengi males and microfilariae, while 9 showed 100 % activity on female worms. The methylene chloride extract of Piper umbellatum leaves was the most active on adult male and female worms (IC50s: 16.63 μg/mL and 35.65 μg/mL, respectively). The three most active extracts on Onchocerca ochengi females were also highly active on Loa loa microfilariae, with IC50s of 35.12 - 13.9 μg/mL. Active extracts were generally more toxic to the worms than to cells and showed no acute toxicity to Balb/c mice. Phytochemical screening revealed the presence of saponins, steroids, tannins and flavanoids in the promising extracts. These results unfold potential sources of novel anti-Onchocerca lead compounds and validate the traditional use of the plants in onchocerciasis treatment.

Development of a Novel Trap for the Collection of Black Flies of the Simulium ochraceum Complex

PubMed Central

Rodríguez-Pérez, Mario A.; Adeleke, Monsuru A.; Burkett-Cadena, Nathan D.; Garza-Hernández, Javier A.; Reyes-Villanueva, Filiberto; Cupp, Eddie W.; Toé, Laurent; Salinas-Carmona, Mario C.; Rodríguez-Ramírez, Américo D.; Katholi, Charles R.; Unnasch, Thomas R.

2013-01-01

Background Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America. Methodology/Principal Findings Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the “Esperanza window trap” showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components) a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors. Conclusions/Significance The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus. PMID:24116169

Spatial and temporal variation in biting rates and parasite transmission potentials of onchocerciasis vectors in Ecuador.

PubMed

Vieira, J C; Brackenboro, L; Porter, C H; Basáñez, M-G; Collins, R C

2005-03-01

The influence of spatial and temporal factors on onchocerciasis transmission by Simulium exiguum s.l. and S. quadrivittatum in Ecuador was investigated to help develop sampling protocols for entomological surveillance of ivermectin programmes. Flies were collected in alternate months (November 1995-November 1996) at four sites each in the hyperendemic communities of San Miguel and El Tigre. A fixed-effects analysis of variance was used to explore the influence on vector abundance of locality, site, month and hour. Infectivity rates detected by dissection and PCR assays were compared. Simulium exiguum s.l. predominated at El Tigre (75%) whereas S. quadrivittatum prevailed at San Miguel (62%). Vector abundance was highest on river banks and outside houses. Biting and infection rates peaked from March to July. Hourly activity patterns were bimodal in S. exiguum but unimodal in S. quadrivittatum. Annual transmission potentials (ATP) for both species combined were 385 and 733 third stage larvae/person in San Miguel and El Tigre respectively, with S. exiguum accounting for 80% of the combined ATP at both localities. We recommend protocols that may maximize detection of parasite transmission. Infection rates thus obtained must be linked with vector density estimates to assess meaningfully host exposure as treatment progresses.

Fifteen Years of Annual Mass Treatment of Onchocerciasis with Ivermectin Have Not Interrupted Transmission in the West Region of Cameroon

PubMed Central

Katabarwa, Moses N.; Eyamba, Albert; Nwane, Philippe; Enyong, Peter; Kamgno, Joseph; Kueté, Thomas; Yaya, Souleymanou; Aboutou, Rosalie; Mukenge, Léonard; Kafando, Claude; Siaka, Coulibaly; Mkpouwoueiko, Salifou; Ngangue, Demanga; Biholong, Benjamin Didier; Andze, Gervais Ondobo

2013-01-01

We followed up the 1996 baseline parasitological and entomological studies on onchocerciasis transmission in eleven health districts in West Region, Cameroon. Annual mass ivermectin treatment had been provided for 15 years. Follow-up assessments which took place in 2005, 2006, and 2011 consisted of skin snips for microfilariae (mf) and palpation examinations for nodules. Follow-up Simulium vector dissections for larval infection rates were done from 2011 to 2012. mf prevalence in adults dropped from 68.7% to 11.4%, and nodule prevalence dropped from 65.9% to 12.1%. The decrease of mf prevalence in children from 29.2% to 8.9% was evidence that transmission was still continuing. mf rates in the follow-up assessments among adults and in children levelled out after a sharp reduction from baseline levels. Only three health districts out of 11 were close to interruption of transmission. Evidence of continuing transmission was also observed in two out of three fly collection sites that had infective rates of 0.19% and 0.18% and ATP of 70 (Foumbot) and 300 (Massangam), respectively. Therefore, halting of annual mass treatment with ivermectin cannot be done after 15 years as it might escalate the risk of transmission recrudescence. PMID:23691275

Willingness to pay for community-based ivermectin distribution: a study of three onchocerciasis-endemic communities in Nigeria.

PubMed

Onwujekwe, O E; Shu, E N; Nwagbo, D; Akpala, C O; Okonkwo, P O

1998-10-01

To determine the willingness to pay (WTP) for local ivermectin distribution in a community financing framework. Contingent valuation in three communities in Nigeria, using randomly selected household heads. WTP was elicited using a bidding game, and for collecting information on the households' socio-economic status, level of knowledge, priority ranking and perception of risk of contracting the disease, structured questionnaires were used. Ordinary least squares (OLS) multiple regression analysis was used to analyse factors associated with WTP. Between 92.1% and 93.3 % of respondents were willing to pay amounts ranging from 5 Naira (US$ 0.06) to 100 Naira (US$ 1.25) (median: 20 Naira, US$ 0.25) in the three communities, more than three times the modelled unit direct cost of distributing ivermectin by the communities themselves. Occupation of the respondent, marital status, average monthly expenditure on health care, manifestations of onchocerciasis, the type of savings scheme embarked on by the respondent, age-group, level of education and type of property were statistically significant (P < 0.05) variables affecting WTP. This study shows that there is WTP for local ivermectin distribution in the three study communities, and that it should be assessed before instituting community-directed treatment with ivermectin.

One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone

PubMed Central

Richards, Frank; Rizzo, Nidia; Espinoza, Carlos Enrique Diaz; Monroy, Zoraida Morales; Valdez, Carol Guillermina Crovella; de Cabrera, Renata Mendizabal; de Leon, Oscar; Zea-Flores, Guillermo; Sauerbrey, Mauricio; Morales, Alba Lucia; Rios, Dalila; Unnasch, Thomas R.; Hassan, Hassan K.; Klein, Robert; Eberhard, Mark; Cupp, Ed; Domínguez, Alfredo

2015-01-01

We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000–2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9–69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ. PMID:26503275

Post-ivermectin encephalopathy in Senegal: a case report.

PubMed

Massi, Daniel Gams; Mansare, Mohamed Lelouma; Traoré, Mariétou; Ndiaye, Moustapha; Diop, Amadou Gallo; Ndiaye, Mouhamadou Mansour

2017-01-01

Ivermectin is an ant parasitic drug used for combating onchocerciasis and lymphatic filariasis. It works by inhibiting the function of neurons and muscles, thus causing paralysis of microfilariae. Side effects of this drug have been reported including post-ivermectin encephalopathy requiring emergency care in hospital. We report the case of a 35 years old patient living in rural areas of Senegal who presented two days after a mistake in administration of a second dose of ivermectin, headaches, altered consciousness and bilateral blindness. The workup revealed brain white matter lesions, abnormal liver function tests and biological inflammation without evidence of Loa loa microfilariae in blood and cerebrospinal fluid. Corticosteroid treatment was administered in emergency and patient recovered despite the persistence of bilateral blindness. Inflammatory process seems to have an important role in the pathophysiology of this encephalopathy. We should therefore carefully control the administration of this drugs.

The Barrie Jones Lecture—Eye care for the neglected population: challenges and solutions

PubMed Central

Rao, G N

2015-01-01

Globally, pockets of ‘neglected populations' do not have access to basic health-care services and carry a much greater risk of blindness and visual impairment. While large-scale public health approaches to control blindness due to vitamin A deficiency, onchocerciasis, and trachoma are successful, other causes of blindness still take a heavy toll in the population. High-quality comprehensive eye care that is equitable is the approach that needs wide-scale application to alleviate this inequity. L V Prasad Eye Institute of India developed a multi-tier pyramidal model of eye care delivery that encompasses all levels from primary to advanced tertiary (quaternary). This has demonstrated the feasibility of ‘Universal Eye Health Coverage' covering promotive, preventive, corrective, and rehabilitative aspects of eye care. Using human resources with competency-based training, effective and cost-effective care could be provided to many disadvantaged people. PMID:25567375

Entomologic considerations in the study of onchocerciasis transmission.

PubMed

Vargas, L; Díaz-Nájera, A

1980-01-01

The entomological resources utilized for a better understanding of Onchocerca volvulus transmission are discussed in this paper. Vector density, anthropohilia, gonotrophic cycyle, parous condition longevity and probability of survival in days after the infectious meal are assessed here in order to integrate an overall picture. The concept of vectorial capacity is developed stressing the quantitative aspects. Parasitism of the black-flies by filariae that are doubtfully identified as O. volvulus is also mentioned here.

Predictors of compliance with community-directed treatment with ivermectin for onchocerciasis control in Kabo area, southwestern Ethiopia.

PubMed

Endale, Adugna; Erko, Berhanu; Weldegebreal, Fitsum; Legesse, Mengistu

2015-02-15

Compliance with annual ivermectin treatment is a major challenge in community-directed treatment with ivermectin (CDTI) implementation. There are individuals who do not comply with the annual mass treatment, which contributes to the continuity for disease transmission. Hence, ensuring high treatment coverage and sustained compliance should be given due emphasis in the control of onchocerciasis. The aim of this study was to determine CDTI compliance rate and predictors of compliance where the CDTI was in its 9(th) round in Kabo area, southwestern Ethiopia. Community-based cross-sectional study was conducted in Kabo area, three weeks after the 9th round of annual ivermectin distribution. Systematic random sampling was used to select head of households and structured, pre-tested questionnaire was used to interview the study participants. Data was analyzed using SPSS version 16. Descriptive statistics was used to compute mean and standard deviation of continuous variables and frequency for categorical variables, while bivariate and multivariate logistic regressions were used to assess the effects of independent variables on the outcome variable. Variables which showed association in multivariate analysis were considered as final predictors of compliance and strength of association was measured through adjusted odds ratio (AOR). A total of 308 respondents (age range 18-70, mean age ± SD, 32.21 ± 9.64) participated in the study. Of these, 249 (80.8%) reported that they took ivermectin during the 9th round annual treatment. Significantly higher rate of treatment compliance was reported by participants age ≥35 years (AOR = 5.48, 95% CI; 1.97 - 15.23), participants who stayed in the area for more than ten years (AOR = 3.86, 95% CI; 1.83- 8.11), participants who perceive that they are at risk of contracting the disease(AOR = 7.05, 2.70- 18.43), participants who perceive community drug distributors (CDDs) are doing their work well (AOR = 2.35 95% CI; 1.15- 4.83) and participants who know at least one CDD in their village (AOR = 2.83, 95% CI; 1.26- 6.40). The majority of the study participants in the present study area complied with ivermectin treatment. Nevertheless, intervention packages should consider factors such as age, residence duration and community's perception of the disease to improve compliance and make drug distribution sustainable.

Recent advances in tropical medicine.

PubMed

Solomon, Anthony W; Nayagam, Shevanthi; Pasvol, Geoffrey

2009-07-01

There have been significant advances in both the classical and neglected tropical diseases, with Guinea worm looking set to be the next disease after smallpox to be eradicated. Aided by a combination of enhanced understanding of the biology of the pathogens, intensification of immunisation activities or mass drug administration, together with the development of synergies with control programmes for co-endemic tropical diseases, polio, lymphatic filariasis, trachoma and onchocerciasis all appear to be in global decline, with good prospects for eventual successful elimination. While the global incidence of new cases of leprosy continues to decrease, the focus of leprosy control efforts has shifted following more widespread recognition that cure of infection does not necessarily prevent disability. Expansion in funding for HIV/AIDS and malaria provides some grounds for optimism about the control of these diseases. However, ongoing education and access remain essential to increasing the uptake of HIV testing and decreasing transmission. Meanwhile, the rise of drug-resistant tuberculosis and malaria is concerning, and the emergence of the highly pathogenic avian influenza A and re-emergence of viruses such as chikungunya and West Nile virus, without significant recent progress in vaccine development, pose additional ongoing challenges to tropical medicine physicians worldwide.

A new methodology for sampling blackflies for the entomological surveillance of onchocerciasis in Brazil

PubMed Central

do Nascimento-Carvalho, Érika S.; Cesário, Raquel de Andrade; do Vale, Vladimir Fazito; Aranda, Arion Tulio; Valente, Ana Carolina dos Santos; Maia-Herzog, Marilza

2017-01-01

The effectiveness of the MosqTent® trap was evaluated in endemic area to onchocerciasis in Brazil. This study seeks to provide subsidies for the monitoring of the onchocerciasis transmission in the country. The study was carried out at the Homoxi and Thirei villages, located in the Yanomami Indigenous Land, in the state of Roraima. This area presents hyperendemicity, high blackflies densities, large population migrations and mining activities. The Homoxi and Thirei villages are assisted by the Brazilian Ministry of Health. To conduct the present study, the village leader, health leaders and the Brazilian Ethics Committee were consulted. Blackflies captures were carried out simultaneously at the Homoxi and Thirei, using systematized methods to allow for comparisons between the traditional Human Landing Catch (HLC) and HLC protected by the MosqTent®. The female blackflies were captured at two equidistant capture stations per locality, by two collectors per station, for five consecutive days. Individuals captured by interval/station/day were counted, identified and maintained at -20°C. The underlying probability distributions and the differences between the methods for the independent sample data were verified in a comparative statistical analysis between the use of the MosqTent® and the HLC. A total of 10,855 antropophilic blackflies were captured by both methodologies. A total of 7,367 (67.87%) blackflies belonging to seven species were captured by MosqTent® —Simulium incrustatum s.l (99.06%); S. guianense s.l (0.74%), S. oyapockense s.l (0.01%), S. exiguum (0.10%), S. metallicum (0.05%), S. ochraceum (0.03%) and S. minusculum s.l (0.01%). Moreover, 3,488 (32.14%) blackflies belonging to four species were captured by HLC—S. incrustatum s.l (98.33%); S. guianense s.l (1.38%), S. oyapockense s.l (0.26%) and S. metallicum (0.03%). The MosqTent® was more effective and efficient when compared to HLC. When comparing total blackflies captured/day, the MosqTent® was more efficient than HLC (p = 0.031) with a means of 799.4 blackflies/day versus 217.6 blackflies/day by HLC. The results demonstrated improved performance and high reliability of the MosqTent® compared to the traditional HLC method. PMID:28727733

A new methodology for sampling blackflies for the entomological surveillance of onchocerciasis in Brazil.

PubMed

Nascimento-Carvalho, Érika S do; Cesário, Raquel de Andrade; do Vale, Vladimir Fazito; Aranda, Arion Tulio; Valente, Ana Carolina Dos Santos; Maia-Herzog, Marilza

2017-01-01

The effectiveness of the MosqTent® trap was evaluated in endemic area to onchocerciasis in Brazil. This study seeks to provide subsidies for the monitoring of the onchocerciasis transmission in the country. The study was carried out at the Homoxi and Thirei villages, located in the Yanomami Indigenous Land, in the state of Roraima. This area presents hyperendemicity, high blackflies densities, large population migrations and mining activities. The Homoxi and Thirei villages are assisted by the Brazilian Ministry of Health. To conduct the present study, the village leader, health leaders and the Brazilian Ethics Committee were consulted. Blackflies captures were carried out simultaneously at the Homoxi and Thirei, using systematized methods to allow for comparisons between the traditional Human Landing Catch (HLC) and HLC protected by the MosqTent®. The female blackflies were captured at two equidistant capture stations per locality, by two collectors per station, for five consecutive days. Individuals captured by interval/station/day were counted, identified and maintained at -20°C. The underlying probability distributions and the differences between the methods for the independent sample data were verified in a comparative statistical analysis between the use of the MosqTent® and the HLC. A total of 10,855 antropophilic blackflies were captured by both methodologies. A total of 7,367 (67.87%) blackflies belonging to seven species were captured by MosqTent® -Simulium incrustatum s.l (99.06%); S. guianense s.l (0.74%), S. oyapockense s.l (0.01%), S. exiguum (0.10%), S. metallicum (0.05%), S. ochraceum (0.03%) and S. minusculum s.l (0.01%). Moreover, 3,488 (32.14%) blackflies belonging to four species were captured by HLC-S. incrustatum s.l (98.33%); S. guianense s.l (1.38%), S. oyapockense s.l (0.26%) and S. metallicum (0.03%). The MosqTent® was more effective and efficient when compared to HLC. When comparing total blackflies captured/day, the MosqTent® was more efficient than HLC (p = 0.031) with a means of 799.4 blackflies/day versus 217.6 blackflies/day by HLC. The results demonstrated improved performance and high reliability of the MosqTent® compared to the traditional HLC method.

One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone.

PubMed

Richards, Frank; Rizzo, Nidia; Diaz Espinoza, Carlos Enrique; Monroy, Zoraida Morales; Crovella Valdez, Carol Guillermina; de Cabrera, Renata Mendizabal; de Leon, Oscar; Zea-Flores, Guillermo; Sauerbrey, Mauricio; Morales, Alba Lucia; Rios, Dalila; Unnasch, Thomas R; Hassan, Hassan K; Klein, Robert; Eberhard, Mark; Cupp, Ed; Domínguez, Alfredo

2015-12-01

We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000-2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9-69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ. © The American Society of Tropical Medicine and Hygiene.

[Medicine and health in the Democratic Republic of Congo: from Independence to the Third Republic].

PubMed

Wembonyama, S; Mpaka, S; Tshilolo, L

2007-10-01

The birth and mortality rates in the Democratic Republic of Congo (DRC), a former Belgian colony, are high, i.e., 48.9/1000 and 17/1000 respectively. The DRC also has one of the highest maternal death rates in the world, i.e., 1289/100,000 live births. Health conditions have not improved since independence. Access to drinking water is limited, living conditions are poor, and food availability in households is low. The mean health services utilization rate in the DRC is estimated to be 0.15 visits/inhabitant/year. The incidence of transmissible diseases is rising. This increase is observed even for illnesses that were under control before independence such as sleeping sickness, onchocerciasis, leprosy, and tuberculosis. One the main causes of mortality and morbidity in the population is malaria that is responsible for the deaths of 150,000 to 250,000 children under the age of 5 every year. The HIV prevalence rate is 4.5% with 1.19 million persons with AIDS and 930,000 orphans whose parents died of AIDS. Other potentially epidemic diseases including bubonic plaque and Ebola hemorrhagic fever are serious threats. Non-transmissible diseases are also on the rise including diabetes, systemic arterial hypertension, cancer and neglected diseases such as sickle cell anemia. To meet these challenges, the country's health authorities have established a program called the Strategy for Reinforcement of the Health System (SRHS). One goal of the SRHS is to develop health zones in order to improve access to quality health care for the whole population.

Efficacy of Three-Week Oxytetracycline or Rifampin Monotherapy Compared with a Combination Regimen against the Filarial Nematode Onchocerca ochengi

PubMed Central

Bah, Germanus S.; Ward, Emma L.; Srivastava, Abhishek; Trees, Alexander J.; Tanya, Vincent N.

2014-01-01

Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a major cause of visual impairment and dermatitis in sub-Saharan Africa. As O. volvulus contains an obligatory bacterial symbiont (Wolbachia), it is susceptible to antibiotic chemotherapy, although current regimens are considered too prolonged for community-level control programs. The aim of this study was to compare the efficacies of oxytetracycline and rifampin, administered separately or in combination, against a close relative of O. volvulus (Onchocerca ochengi) in cattle. Six animals per group were treated with continuous or intermittent oxytetracycline regimens, and effects on adult worm viability, dermal microfilarial loads, and Wolbachia density in worm tissues were assessed. Subsequently, the efficacies of 3-week regimens of oxytetracycline and rifampin alone and a combination regimen were compared, and rifampin levels in plasma and skin were quantified. A 6-month regimen of oxytetracycline with monthly dosing was strongly adulticidal, while 3-week and 6-week regimens exhibited weaker adulticidal effects. However, all three regimens achieved >2-log reductions in microfilarial load. In contrast, rifampin monotherapy and oxytetracycline-rifampin duotherapy failed to induce substantive reductions in either adult worm burden or microfilarial load, although a borderline effect on Wolbachia density was observed following duotherapy. Dermal rifampin levels were maintained above the MIC for >24 h after a single intravenous dose. We conclude that oxytetracycline-rifampin duotherapy is less efficacious against O. ochengi than oxytetracycline alone. Further studies will be required to determine whether rifampin reduces oxytetracycline bioavailability in this system, as suggested by human studies using other tetracycline-rifampin combinations. PMID:24247133

Efficacy of three-week oxytetracycline or rifampin monotherapy compared with a combination regimen against the filarial nematode Onchocerca ochengi.

PubMed

Bah, Germanus S; Ward, Emma L; Srivastava, Abhishek; Trees, Alexander J; Tanya, Vincent N; Makepeace, Benjamin L

2014-01-01

Onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, is a major cause of visual impairment and dermatitis in sub-Saharan Africa. As O. volvulus contains an obligatory bacterial symbiont (Wolbachia), it is susceptible to antibiotic chemotherapy, although current regimens are considered too prolonged for community-level control programs. The aim of this study was to compare the efficacies of oxytetracycline and rifampin, administered separately or in combination, against a close relative of O. volvulus (Onchocerca ochengi) in cattle. Six animals per group were treated with continuous or intermittent oxytetracycline regimens, and effects on adult worm viability, dermal microfilarial loads, and Wolbachia density in worm tissues were assessed. Subsequently, the efficacies of 3-week regimens of oxytetracycline and rifampin alone and a combination regimen were compared, and rifampin levels in plasma and skin were quantified. A 6-month regimen of oxytetracycline with monthly dosing was strongly adulticidal, while 3-week and 6-week regimens exhibited weaker adulticidal effects. However, all three regimens achieved >2-log reductions in microfilarial load. In contrast, rifampin monotherapy and oxytetracycline-rifampin duotherapy failed to induce substantive reductions in either adult worm burden or microfilarial load, although a borderline effect on Wolbachia density was observed following duotherapy. Dermal rifampin levels were maintained above the MIC for >24 h after a single intravenous dose. We conclude that oxytetracycline-rifampin duotherapy is less efficacious against O. ochengi than oxytetracycline alone. Further studies will be required to determine whether rifampin reduces oxytetracycline bioavailability in this system, as suggested by human studies using other tetracycline-rifampin combinations.

International Vision Care: Issues and Approaches.

PubMed

Khanna, Rohit C; Marmamula, Srinivas; Rao, Gullapalli N

2017-09-15

Globally, 32.4 million individuals are blind and 191 million have moderate or severe visual impairment (MSVI); 80% of cases of blindness and MSVI are avoidable. However, great efforts are needed to tackle blindness and MSVI, as eye care in most places is delivered in isolation from and without significant integration with general health sectors. Success stories, including control of vitamin A deficiency, onchocerciasis, and trachoma, showed that global partnerships, multisectoral collaboration, public-private partnerships, corporate philanthropy, support from nongovernmental organizations-both local and international-and governments are responsible for the success of these programs. Hence, the World Health Organization's universal eye health global action plan for 2014-2019 has a goal of reducing the public health problem of blindness and ensuring access to comprehensive eye care; the plan aims to integrate eye health into health systems, thus providing universal eye health coverage (UEHC). This article discusses the challenges faced by low- and middle-income countries in strengthening the six building blocks of the health system. It discusses how the health systems in these countries need to be geared toward tackling the issues of emerging noncommunicable eye diseases, existing infectious diseases, and the common causes of blindness and visual impairment, such as cataract and refractive error. It also discusses how some of the comprehensive eye care models in the developing world have addressed these challenges. Moving ahead, if we are to achieve UEHC, we need to develop robust, sustainable, good-quality, comprehensive eye care programs throughout the world, focusing on the areas of greatest need. We also need to develop public health approaches for more complex problems such as diabetic retinopathy, glaucoma, childhood blindness, corneal blindness, and low vision. There is also a great need to train high-level human resources of all cadres in adequate numbers and quality. In addition to this, we need to exploit the benefits of modern technological innovations in information, communications, biomedical technology, and other domains to enhance quality of, access to, and equity in eye care.

Health-related biotechnologies for infectious disease control in Africa: Ethical, Legal and Social Implications (ELSI) of transfer and development.

PubMed

Sommerfeld, J; Oduola, A M J

2007-01-01

The African continent is disproportionately affected by infectious diseases. Malaria, HIV/AIDS, tuberculosis, and more "neglected" diseases including African trypanosomiasis, Buruli ulcer, leishmaniasis, onchocerciasis and trachoma continue to dramatically impact social and economic development on the continent. Health biotechnologies provide potential to develop effective strategies for the fight against the vicious circle of poverty and infections by helping in the development and improvement of novel affordable drugs, diagnostics and vaccines against these diseases. As the prospects of this emerging biotechnology research and deployment of its products become a reality in Africa, there is a need to consider the ethical, legal and social implications of both the scientific and technological advances and their use in the communities. The article provides a short overview of the potential values of biotechnology, issues involved in its transfer and presents the rationale, design and recommendations of the international workshop/symposium held in April 2005 at the International Institute for Tropical Agriculture (IITA) in Ibadan, Nigeria.

Identification and prioritization of novel anti-Wolbachia chemotypes from screening a 10,000-compound diversity library

PubMed Central

Johnston, Kelly L.; Cook, Darren A. N.; Berry, Neil G.; David Hong, W.; Clare, Rachel H.; Goddard, Megan; Ford, Louise; Nixon, Gemma L.; O’Neill, Paul M.; Ward, Stephen A.; Taylor, Mark J.

2017-01-01

Lymphatic filariasis and onchocerciasis are two important neglected tropical diseases (NTDs) that cause severe disability. Control efforts are hindered by the lack of a safe macrofilaricidal drug. Targeting the Wolbachia bacterial endosymbionts in these parasites with doxycycline leads to a macrofilaricidal outcome, but protracted treatment regimens and contraindications restrict its widespread implementation. The Anti-Wolbachia consortium aims to develop improved anti-Wolbachia drugs to overcome these barriers. We describe the first screening of a large, diverse compound library against Wolbachia. This whole-organism screen, streamlined to reduce bottlenecks, produced a hit rate of 0.5%. Chemoinformatic analysis of the top 50 hits led to the identification of six structurally diverse chemotypes, the disclosure of which could offer interesting avenues of investigation to other researchers active in this field. An example of hit-to-lead optimization is described to further demonstrate the potential of developing these high-quality hit series as safe, efficacious, and selective anti-Wolbachia macrofilaricides. PMID:28959730

Onchocerciasis in Venezuela: prevalence of microfilaraemia in Amerindians and morphological characteristics of the microfilariae from the Upper Orinoco Focus.

PubMed

Botto, C; Arango, M; Yarzábal, L

1984-09-01

Data are presented on microfilaraemia in 191 Yanomami Amerindians from two areas of Venezuela's Upper Orinoco Basin, where an endemic focus of onchocerciasis has been recently detected. Onchocerca microfilariae were found in the blood of 12.6% of the persons examined. In the village with the higher number of examined individuals (N = 162), the prevalence of microfilaraemia in the age groups covaried with the prevalence of microfilariae in the skin and with the parasite load (mf/mg of skin). A positive correlation was found between age and these three variables. The prevalence of Onchocerca microfilaraemia in the Upper Orinoco focus is high, and may be related to the ability of the strain to invade the blood stream. Morphobiometric characteristics of the Onchocerca microfilariae isolated from human blood are similar to those of O. volvulus fixed in formalin from skin and from the uterus of female O. volvulus worms. All have a very short cephalic space. Comparisons with the entity from the Upper Caura river designated as Microfilaria bolivarensis were also made. It was concluded that there are no valid biometric differences in thick blood smears between microfilaria bolivarensis and microfilaria of O. volvulus from the Upper Orinoco deme. A more striking difference may be in the concentration of microfilariae observed in the blood, which in one case of mf. bolivarensis was more than forty times the highest number recorded for microfilaria O. volvulus in Parima.

Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis

PubMed Central

Sharma, Raman; Jayoussi, Ghaith Al; Tyrer, Hayley E.; Gamble, Joanne; Hayward, Laura; Guimaraes, Ana F.; Davies, Jill; Waterhouse, David; Cook, Darren A. N.; Myhill, Laura J.; Clare, Rachel H.; Cassidy, Andrew; Steven, Andrew; Johnston, Kelly L.; Ford, Louise; Turner, Joseph D.; Ward, Stephen A.; Taylor, Mark J.

2016-01-01

Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25–40 mg/Kg regimen is bioequivalent to a clinically effective 100–200 mg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28 day 25 mg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis. PMID:26996237

Soil transmitted helminths and scabies in Zanzibar, Tanzania following mass drug administration for lymphatic filariasis - a rapid assessment methodology to assess impact

PubMed Central

2012-01-01

Background Ivermectin and albendazole are used in annual mass drug administration (MDA) for the lymphatic filariasis elimination programmes in African countries co-endemic for onchocerciasis, but have additional impact on soil transmitted helminths and the ectoparasitic mite which causes scabies. Assessing these collateral impacts at scale is difficult due to the insensitivity of available parasite detection techniques. Methods The numbers of cases diagnosed with intestinal helminths and scabies and who received prescriptions for treatment were evaluated in 50 health centres in Zanzibar. Records were examined from 2000, prior to the initiation of MDA to 2005, after six rounds of MDA for lymphatic filariasis had taken place. Results Health centre records showed a consistent decline in the number of cases of intestinal helminths and scabies diagnosed by community health workers in Zanzibar and the number of prescriptions issued across five age groups. A 90-98% decline in soil transmitted helminths and 68-98% decline in scabies infections were recorded. Poisson regression models aggregated to both the island-level and district-level indicated that the decline was statistically significant. Conclusions The described method of examining health centre records has the potential for use on a large scale, despite limitations, as a rapid method to evaluate the impacts resulting from both lymphatic filariasis and onchocerciasis MDA. This would result in a reduction in the need for parasitological evaluations to determine prevalence and intensity. PMID:23259465

Immunotherapy with mutated onchocystatin fails to enhance the efficacy of a sub-lethal oxytetracycline regimen against Onchocerca ochengi.

PubMed

Bah, Germanus S; Tanya, Vincent N; Makepeace, Benjamin L

2015-08-15

Human onchocerciasis (river blindness), caused by the filarial nematode Onchocerca volvulus, has been successfully controlled by a single drug, ivermectin, for over 25 years. Ivermectin prevents the disease symptoms of severe itching and visual impairment by killing the microfilarial stage, but does not eliminate the adult parasites, necessitating repeated annual treatments. Mass drug administration with ivermectin does not always break transmission in forest zones and is contraindicated in individuals heavily co-infected with Loa loa, while reports of reduced drug efficacy in Ghana and Cameroon may signal the development of resistance. An alternative treatment for onchocerciasis involves targeting the essential Wolbachia symbiont with tetracycline or its derivatives, which are adulticidal. However, implementation of antibiotic therapy has not occurred on a wide scale due to the prolonged treatment regimen required (several weeks). In the bovine Onchocerca ochengi system, it has been shown previously that prolonged oxytetracycline therapy increases eosinophil counts in intradermal nodules, which kill the adult worms by degranulating on their surface. Here, in an "immunochemotherapeutic" approach, we sought to enhance the efficacy of a short, sub-lethal antibiotic regimen against O. ochengi by prior immunotherapy targeting onchocystatin, an immunomodulatory protein located in the adult female worm cuticle. A key asparagine residue in onchocystatin was mutated to ablate immunomodulatory activity, which has been demonstrated previously to markedly improve the protective efficacy of this vaccine candidate when used as an immunoprophylactic. The immunochemotherapeutic regimen was compared with sub-lethal oxytetracycline therapy alone; onchocystatin immunotherapy alone; a gold-standard prolonged, intermittent oxytetracycline regimen; and no treatment (negative control) in naturally infected Cameroonian cattle. Readouts were collected over one year and comprised adult worm viability, dermal microfilarial density, anti-onchocystatin IgG in sera, and eosinophil counts in nodules. Only the gold-standard antibiotic regimen achieved significant killing of adult worms, a profound reduction in microfilarial load, and a sustained increase in local tissue eosinophilia. A small but statistically significant elevation in anti-onchocystatin IgG was observed for several weeks after immunisation in the immunotherapy-only group, but the antibody response in the immunochemotherapy group was more variable. At 12 weeks post-treatment, only a transient and non-significant increase in eosinophil counts was apparent in the immunochemotherapy group. We conclude that the addition of onchocystatin immunotherapy to a sub-lethal antibiotic regimen is insufficient to induce adulticidal activity, although with booster immunisations or the targeting of additional filarial immunomodulatory proteins, the efficacy of this strategy could be strengthened. Copyright © 2015 Elsevier B.V. All rights reserved.

Community perceptions on the community-directed treatment and school-based approaches for the control of schistosomiasis and soil-transmitted helminthiasis among school-age children in Lushoto District, Tanzania.

PubMed

Massa, K; Magnussen, P; Sheshe, A; Ntakamulenga, R; Ndawi, B; Olsen, A

2009-01-01

The success of the Community-Directed Treatment (ComDT) approach in the control of onchocerciasis and filariasis has caught the attention of other disease control programmes. In this study the ComDT approach was implemented and compared with the school-based approach for control of schistosomiasis and soil-transmitted helminthiasis among school-age children in Lushoto District, Tanzania. This was a qualitative study, consisting of in-depth interviews with village leaders, community drug distributors (CDDs) and schoolteachers, as well as focus group discussions with separate groups of mothers and fathers to assess the perceptions and experiences of the villagers on the implementation of the two approaches. It was found that the villagers accepted the ComDT approach and took the responsibility of selecting the CDDs, organizing and implementing their own method of distributing drugs to the school-age children in their villages. The ComDT approach was well received and was successfully implemented in the villages. Although the villagers pointed out the limitation in reaching the non-enrolled children in the school-based approach, they also expressed satisfaction with this approach. This study suggests that the ComDT approach is well accepted and can be implemented effectively to ensure better coverage of especially non-enrolled school-age children.

Development of a highly sensitive loop-mediated isothermal amplification (LAMP) method for the detection of Loa loa.

PubMed

Fernández-Soto, Pedro; Mvoulouga, Prosper Obolo; Akue, Jean Paul; Abán, Julio López; Santiago, Belén Vicente; Sánchez, Miguel Cordero; Muro, Antonio

2014-01-01

The filarial parasite Loa loa, the causative agent of loiasis, is endemic in Central and Western Africa infecting 3-13 million people. L. loa has been associated with fatal encephalopathic reactions in high Loa-infected individuals receiving ivermectin during mass drug administration programs for the control of onchocerciasis and lymphatic filariasis. In endemic areas, the only diagnostic method routinely used is the microscopic examination of mid-day blood samples by thick blood film. Improved methods for detection of L. loa are needed in endemic regions with limited resources, where delayed diagnosis results in high mortality. We have investigated the use of a loop-mediated isothermal amplification (LAMP) assay to facilitate rapid, inexpensive, molecular diagnosis of loiasis. Primers for LAMP were designed from a species-specific repetitive DNA sequence from L. loa retrieved from GenBank. Genomic DNA of a L. loa adult worm was used to optimize the LAMP conditions using a thermocycler or a conventional heating block. Amplification of DNA in the LAMP mixture was visually inspected for turbidity as well as addition of fluorescent dye. LAMP specificity was evaluated using DNA from other parasites; sensitivity was evaluated using DNA from L. loa 10-fold serially diluted. Simulated human blood samples spiked with DNA from L. loa were also tested for sensitivity. Upon addition of fluorescent dye, all positive reactions turned green while the negative controls remained orange under ambient light. After electrophoresis on agarose gels, a ladder of multiple bands of different sizes could be observed in positive samples. The detection limit of the assay was found to be as little as 0.5 ag of L. loa genomic DNA when using a heating block. We have designed, for the first time, a highly sensitive LAMP assay for the detection of L. loa which is potentially adaptable for field diagnosis and disease surveillance in loiasis-endemic areas.

Development of a Highly Sensitive Loop-Mediated Isothermal Amplification (LAMP) Method for the Detection of Loa loa

PubMed Central

Fernández-Soto, Pedro; Mvoulouga, Prosper Obolo; Akue, Jean Paul; Abán, Julio López; Santiago, Belén Vicente; Sánchez, Miguel Cordero; Muro, Antonio

2014-01-01

The filarial parasite Loa loa, the causative agent of loiasis, is endemic in Central and Western Africa infecting 3–13 million people. L. loa has been associated with fatal encephalopathic reactions in high Loa-infected individuals receiving ivermectin during mass drug administration programs for the control of onchocerciasis and lymphatic filariasis. In endemic areas, the only diagnostic method routinely used is the microscopic examination of mid-day blood samples by thick blood film. Improved methods for detection of L. loa are needed in endemic regions with limited resources, where delayed diagnosis results in high mortality. We have investigated the use of a loop-mediated isothermal amplification (LAMP) assay to facilitate rapid, inexpensive, molecular diagnosis of loiasis. Primers for LAMP were designed from a species-specific repetitive DNA sequence from L. loa retrieved from GenBank. Genomic DNA of a L. loa adult worm was used to optimize the LAMP conditions using a thermocycler or a conventional heating block. Amplification of DNA in the LAMP mixture was visually inspected for turbidity as well as addition of fluorescent dye. LAMP specificity was evaluated using DNA from other parasites; sensitivity was evaluated using DNA from L. loa 10-fold serially diluted. Simulated human blood samples spiked with DNA from L. loa were also tested for sensitivity. Upon addition of fluorescent dye, all positive reactions turned green while the negative controls remained orange under ambient light. After electrophoresis on agarose gels, a ladder of multiple bands of different sizes could be observed in positive samples. The detection limit of the assay was found to be as little as 0.5 ag of L. loa genomic DNA when using a heating block. We have designed, for the first time, a highly sensitive LAMP assay for the detection of L. loa which is potentially adaptable for field diagnosis and disease surveillance in loiasis-endemic areas. PMID:24722638

Can coverage of schistosomiasis and soil transmitted helminthiasis control programmes targeting school-aged children be improved? New approaches.

PubMed

Massa, K; Olsen, A; Sheshe, A; Ntakamulenga, R; Ndawi, B; Magnussen, P

2009-11-01

Control programmes generally use a school-based strategy of mass drug administration to reduce morbidity of schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged populations. The success of school-based programmes depends on treatment coverage. The community-directed treatment (ComDT) approach has been implemented in the control of onchocerciasis and lymphatic filariasis in Africa and improves treatment coverage. This study compared the treatment coverage between the ComDT approach and the school-based treatment approach, where non-enrolled school-aged children were invited for treatment, in the control of schistosomiasis and STH among enrolled and non-enrolled school-aged children. Coverage during the first treatment round among enrolled children was similar for the two approaches (ComDT: 80.3% versus school: 82.1%, P=0.072). However, for the non-enrolled children the ComDT approach achieved a significantly higher coverage than the school-based approach (80.0 versus 59.2%, P<0.001). Similar treatment coverage levels were attained at the second treatment round. Again, equal levels of treatment coverage were found between the two approaches for the enrolled school-aged children, while the ComDT approach achieved a significantly higher coverage in the non-enrolled children. The results of this study showed that the ComDT approach can obtain significantly higher treatment coverage among the non-enrolled school-aged children compared to the school-based treatment approach for the control of schistosomiasis and STH.

Interruption of Transmission of Onchocerca volvulus in the Southern Chiapas Focus, México

PubMed Central

Rodríguez-Pérez, Mario A.; Domínguez-Vázquez, Alfredo; Unnasch, Thomas R.; Hassan, Hassan K.; Arredondo-Jiménez, Juan I.; Orozco-Algarra, María Eugenia; Rodríguez-Morales, Kristel B.; Rodríguez-Luna, Isabel C.; Prado-Velasco, Francisco Gibert

2013-01-01

Background The Southern Chiapas focus of onchocerciasis in Southern Mexico represents one of the major onchocerciasis foci in Latin America. All 559 endemic communities of this focus have undergone semi-annual mass treatment with ivermectin since 1998. In 50 communities of this focus, ivermectin frequency shifted from twice to four times a year in 2003; an additional 113 communities were added to the quarterly treatment regimen in 2009 to achieve a rapid suppression of transmission. Methodology/Principal findings In-depth epidemiologic and entomologic assessments were performed in six sentinel communities (which had undergone 2 rounds of ivermectin treatment per year) and three extra-sentinel communities (which had undergone 4 rounds of ivermectin treatment per year). None of the 67,924 Simulium ochraceum s.l. collected from this focus during the dry season of 2011 were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.06/2,000 flies examined. Serological assays testing for Onchocerca volvulus exposure conducted on 4,230 children 5 years of age and under (of a total population of 10,280 in this age group) revealed that 2/4,230 individuals were exposed to O. volvulus (0.05%; one sided 95% confidence interval = 0.08%). Conclusions/Significance The in-depth epidemiological and entomological findings from the Southern Chiapas focus meet the criteria for interruption of transmission developed by the international community. PMID:23556018

Elimination of Onchocerciasis from Mexico.

PubMed

Rodríguez-Pérez, Mario A; Fernández-Santos, Nadia A; Orozco-Algarra, María E; Rodríguez-Atanacio, José A; Domínguez-Vázquez, Alfredo; Rodríguez-Morales, Kristel B; Real-Najarro, Olga; Prado-Velasco, Francisco G; Cupp, Eddie W; Richards, Frank O; Hassan, Hassan K; González-Roldán, Jesús F; Kuri-Morales, Pablo A; Unnasch, Thomas R

2015-01-01

Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS) surveys were undertaken which employed entomological indicators to check for transmission recrudescence. In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP) was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population. The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico.

The mermithid species Isomermis lairdi (Nematoda, Mermithidae), previously only known in Africa, found in Europe

PubMed Central

Gradinarov, Denis

2014-01-01

Abstract The present work contributs to the knowledge on the aquatic mermithids (Nematoda, Mermithidae) occurring in black flies – an insufficiently studied group of parasitic nematodes. Isomermis lairdi Mondet, Poinar & Bernadou, 1977, described from larvae of Simulium damnosum Theobald, 1903 in Western Africa, is reported to occur in Bulgaria. The species was isolated from larvae of Simulium ornatum Meigen, 1818 in a local population of simuliids in a mountain stream near Jeleznitsa Village, Sofia district. Postparasitic juveniles of mermithids were obtained from the hosts and reared to the adult stage. The species was identified by morphological and morphometrical characters of postparasitic juveniles, and of male and female individuals. In the summer of 2012 a relatively high rate of mermithid infection in a local host population was detected (prevalence up to 44.1%). In August of the next year host abundance had considerably declined and other simuliid species, Simulium variegatum Meigen, 1818 and Simulium reptans (Linnaeus, 1758), predominated in the investigated locality. In West Africa, Isomermis lairdi is considered to be a potential biological agent for reducing the population density of the Simulium damnosum complex – the main vector of human onchocerciasis. In Europe, species of the Simulium ornatum complex are among the vectors of onchocerciasis of cattle and deer. The mermithids presumably play a certain role in the epidemiology of these diseases. A brief discussion on the taxonomy of the genus Isomermis Coman, 1953, and of the feasibility of molecular methods in mermithid taxonomy is provided. The species Isomermis lairdi is reported for the first time from Europe. PMID:25493063

Combinations of registered drugs reduce treatment times required to deplete Wolbachia in the Litomosoides sigmodontis mouse model

PubMed Central

Specht, Sabine; Arriens, Sandra; Hübner, Marc P.; Klarmann-Schulz, Ute; Koschel, Marianne; Sternberg, Sonja; Martin, Coralie; Taylor, Mark J.; Hoerauf, Achim

2018-01-01

Filarial parasites can be targeted by antibiotic treatment due to their unique endosymbiotic relationship with Wolbachia bacteria. This finding has led to successful treatment strategies in both, human onchocerciasis and lymphatic filariasis. A 4–6 week treatment course using doxycycline results in long-term sterility and safe macrofilaricidal activity in humans. However, current treatment times and doxycycline contraindications in children and pregnant women preclude widespread administration of doxycycline in public health control programs; therefore, the search for shorter anti-wolbachial regimens is a focus of ongoing research. We have established an in vivo model for compound screening, using mice infected with Litomosoides sigmodontis. We could show that gold standard doxycycline treatment did not only deplete Wolbachia, it also resulted in a larval arrest. In this model, combinations of registered antibiotics were tested for their anti-wolbachial activity. Administration of rifamycins in combination with doxycycline for 7 days successfully depleted Wolbachia by > 2 log (>99% reduction) and thus resulted in a significant reduction of the treatment duration. Using a triple combination of a tetracycline (doxycycline or minocycline), a rifamycin and a fluoroquinolone (moxifloxacin) led to an even greater shortening of the treatment time. Testing all double combinations that could be derived from the triple combinations revealed that the combination of rifapentine (15mg/kg) and moxifloxacin (2 x 200mg/kg) showed the strongest reduction of treatment time in intraperitoneal and also oral administration routes. The rifapentine plus moxifloxacin combination was equivalent to the triple combination with additional doxycycline (>99% Wolbachia reduction). These investigations suggest that it is possible to shorten anti-wolbachial treatment times with combination treatments in order to achieve the target product profile (TPP) requirements for macrofilaricidal drugs of no more than 7–10 days of treatment. PMID:29300732

Combinations of registered drugs reduce treatment times required to deplete Wolbachia in the Litomosoides sigmodontis mouse model.

PubMed

Specht, Sabine; Pfarr, Kenneth M; Arriens, Sandra; Hübner, Marc P; Klarmann-Schulz, Ute; Koschel, Marianne; Sternberg, Sonja; Martin, Coralie; Ford, Louise; Taylor, Mark J; Hoerauf, Achim

2018-01-01

Filarial parasites can be targeted by antibiotic treatment due to their unique endosymbiotic relationship with Wolbachia bacteria. This finding has led to successful treatment strategies in both, human onchocerciasis and lymphatic filariasis. A 4-6 week treatment course using doxycycline results in long-term sterility and safe macrofilaricidal activity in humans. However, current treatment times and doxycycline contraindications in children and pregnant women preclude widespread administration of doxycycline in public health control programs; therefore, the search for shorter anti-wolbachial regimens is a focus of ongoing research. We have established an in vivo model for compound screening, using mice infected with Litomosoides sigmodontis. We could show that gold standard doxycycline treatment did not only deplete Wolbachia, it also resulted in a larval arrest. In this model, combinations of registered antibiotics were tested for their anti-wolbachial activity. Administration of rifamycins in combination with doxycycline for 7 days successfully depleted Wolbachia by > 2 log (>99% reduction) and thus resulted in a significant reduction of the treatment duration. Using a triple combination of a tetracycline (doxycycline or minocycline), a rifamycin and a fluoroquinolone (moxifloxacin) led to an even greater shortening of the treatment time. Testing all double combinations that could be derived from the triple combinations revealed that the combination of rifapentine (15mg/kg) and moxifloxacin (2 x 200mg/kg) showed the strongest reduction of treatment time in intraperitoneal and also oral administration routes. The rifapentine plus moxifloxacin combination was equivalent to the triple combination with additional doxycycline (>99% Wolbachia reduction). These investigations suggest that it is possible to shorten anti-wolbachial treatment times with combination treatments in order to achieve the target product profile (TPP) requirements for macrofilaricidal drugs of no more than 7-10 days of treatment.

Rapid Suppression of Onchocerca volvulus Transmission in Two Communities of the Southern Chiapas Focus, Mexico, Achieved by Quarterly Treatments with Mectizan

PubMed Central

Rodríguez-Pérez, Mario A.; Lutzow-Steiner, Miguel A.; Segura-Cabrera, Aldo; Lizarazo-Ortega, Cristian; Domínguez-Vázquez, Alfredo; Sauerbrey, Mauricio; Richards, Frank; Unnasch, Thomas R.; Hassan, Hassan K.; Hernández-Hernández, Raymundo

2008-01-01

The impact of quarterly Mectizan (ivermectin) treatments on transmission, microfiladermia, and ocular lesions was evaluated in two formerly hyperendemic communities (Las Golondrinas and Las Nubes II) located in the main endemic focus for onchocerciasis in Southern Chiapas, Mexico. The data suggest that Onchocerca volvulus transmission has been suppressed after elimination of microfiladermia in these two communities. Increasing the frequency of Mectizan treatment to four times per year appears to have resulted in the rapid suppression of transmission in communities with residual transmission. PMID:18689630

The mitogenome of Onchocerca volvulus from the Brazilian Amazonia focus.

PubMed

Crainey, James L; Silva, Túllio R R da; Encinas, Fernando; Marín, Michel A; Vicente, Ana Carolina P; Luz, Sérgio L B

2016-01-01

We report here the first complete mitochondria genome of Onchocerca volvulus from a focus outside of Africa. An O. volvulus mitogenome from the Brazilian Amazonia focus was obtained using a combination of high-throughput and Sanger sequencing technologies. Comparisons made between this mitochondrial genome and publicly available mitochondrial sequences identified 46 variant nucleotide positions and suggested that our Brazilian mitogenome is more closely related to Cameroon-origin mitochondria than West African-origin mitochondria. As well as providing insights into the origins of Latin American onchocerciasis, the Brazilian Amazonia focus mitogenome may also have value as an epidemiological resource.

Epidemiology of Tropical Neglected Diseases in Ecuador in the Last 20 Years

PubMed Central

Cartelle Gestal, Monica; Holban, Alina Maria; Escalante, Santiago; Cevallos, Marcelo

2015-01-01

Background Tropical and zoonotic diseases are major problems in developing countries like Ecuador. Poorly designed houses, the high proportion of isolated indigenous population and under developed infrastructure represent a fertile environment for vectors to proliferate. Control campaigns in Ecuador over the years have had varying success, depending on the disease and vectors targeted. Aims In our study we analyse the current situation of some neglected diseases in Ecuador and the efficiency of the control campaigns (by measuring changes in numbers of cases reported) that the Ecuadorian government has been running to limit the spread of these infectious and parasitic diseases. Results Our study reveals that Brucellosis, Chagas Disease, Rabies and Onchocerciasis have been controlled, but small outbreaks are still detected in endemic areas. Leptospirosis and Echinococcosis have been increasing steadily in recent years in Ecuador since the first records. The same increase has been reported world-wide also. Better diagnosis has resulted in a higher number of cases being identified, particularly with regard to the linking of outdoor activities and contact with farm animals as contributing vectors. Improvements in diagnosis are due to regular professional training, implementation of automatized systems, establishing diagnosis protocols and the creation of an epidemiological vigilance network that acts as soon as a case is reported. Conclusion Control campaigns performed in Ecuador have been successful in recent years, although natural phenomena limit their efficiency. Leptospirosis and Echinococcosis infections remain a growing problem in Ecuador as it is worldwide. PMID:26394405

Epidemiology of Tropical Neglected Diseases in Ecuador in the Last 20 Years.

PubMed

Cartelle Gestal, Monica; Holban, Alina Maria; Escalante, Santiago; Cevallos, Marcelo

2015-01-01

Tropical and zoonotic diseases are major problems in developing countries like Ecuador. Poorly designed houses, the high proportion of isolated indigenous population and under developed infrastructure represent a fertile environment for vectors to proliferate. Control campaigns in Ecuador over the years have had varying success, depending on the disease and vectors targeted. In our study we analyse the current situation of some neglected diseases in Ecuador and the efficiency of the control campaigns (by measuring changes in numbers of cases reported) that the Ecuadorian government has been running to limit the spread of these infectious and parasitic diseases. Our study reveals that Brucellosis, Chagas Disease, Rabies and Onchocerciasis have been controlled, but small outbreaks are still detected in endemic areas. Leptospirosis and Echinococcosis have been increasing steadily in recent years in Ecuador since the first records. The same increase has been reported world-wide also. Better diagnosis has resulted in a higher number of cases being identified, particularly with regard to the linking of outdoor activities and contact with farm animals as contributing vectors. Improvements in diagnosis are due to regular professional training, implementation of automatized systems, establishing diagnosis protocols and the creation of an epidemiological vigilance network that acts as soon as a case is reported. Control campaigns performed in Ecuador have been successful in recent years, although natural phenomena limit their efficiency. Leptospirosis and Echinococcosis infections remain a growing problem in Ecuador as it is worldwide.

Global trends in neglected tropical disease control and elimination: impact on child health.

PubMed

Barry, Meagan A; Simon, Gregory G; Mistry, Neeraj; Hotez, Peter J

2013-08-01

The neglected tropical diseases (NTDs) are a group of 17 lesser known chronic infections which predominantly affect poor and disenfranchised communities. There are a number of NTDs that cause significant global morbidity in children, including the three major soil transmitted helminth (STH) infections (ascariasis, trichuriasis and hookworm infection), schistosomiasis and trachoma. These NTDs, together with lymphatic filariasis and onchocerciasis, are currently being targeted for global control and elimination through mass drug administration (MDA) campaigns. They represent the most common NTDs and share significant geographical overlap. Additionally, many individuals are polyparasitised with more than a single NTD. Integrated NTD control and elimination MDA programmes offer safe and efficacious treatments for all seven NTDs. However, the current global level of MDA coverage for the leading childhood NTDs, that is, STH infections, schistosomiasis and trachoma, remains well under 50%. Limiting factors for global coverage include insufficient global financial support, drug donation capacity of pharmaceutical companies and targeting school age children to the exclusion of other age groups in need of treatment, such as preschool age children. There is also a need for development of novel prevention and treatment modalities, such as next-generation small molecule drugs and vaccines. Efforts are underway to harness the momentum of a 2012 London Declaration on NTDs and a 2013 World Health Assembly (WHA) resolution as a means to control or in some cases eliminate by 2020 these NTDs that affect children worldwide.

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases.

PubMed

Hollingsworth, T Déirdre; Adams, Emily R; Anderson, Roy M; Atkins, Katherine; Bartsch, Sarah; Basáñez, María-Gloria; Behrend, Matthew; Blok, David J; Chapman, Lloyd A C; Coffeng, Luc; Courtenay, Orin; Crump, Ron E; de Vlas, Sake J; Dobson, Andy; Dyson, Louise; Farkas, Hajnal; Galvani, Alison P; Gambhir, Manoj; Gurarie, David; Irvine, Michael A; Jervis, Sarah; Keeling, Matt J; Kelly-Hope, Louise; King, Charles; Lee, Bruce Y; Le Rutte, Epke A; Lietman, Thomas M; Ndeffo-Mbah, Martial; Medley, Graham F; Michael, Edwin; Pandey, Abhishek; Peterson, Jennifer K; Pinsent, Amy; Porco, Travis C; Richardus, Jan Hendrik; Reimer, Lisa; Rock, Kat S; Singh, Brajendra K; Stolk, Wilma; Swaminathan, Subramanian; Torr, Steve J; Townsend, Jeffrey; Truscott, James; Walker, Martin; Zoueva, Alexandra

2015-12-09

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination 'as a public health problem' when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models' predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.

[The road to elimination: an overview of neglected infectious diseases in Latin America and the Caribbean].

PubMed

Ault, Steven Kenyon; Catalá Pascual, Laura; Grados-Zavala, Maria Elena; Gonzálvez García, Guillermo; Castellanos, Luis Gerardo

2014-04-01

Neglected infectious diseases (NID) affect mainly isolated populations living in isolation and in poor socioeconomic conditions. These diseases, by their chronic and silent nature, often affect communities with a weak political voice. This translates into very little attention or political priority; which is reflected in minimal and insufficient preventive measures, monitoring and control. However, there is evidence this situation is changing favorably in some countries of the Americas. In recent years, several resolutions (official agreement of the member countries of the Pan American Health Organization / World Health Organization-PAHO / WHO), regional and global agreements on public health; with a greater commitment from the pharmaceutical industry, and other donors and international partners in combination with the development and use of integrated action plans have allowed countries to intensify public interventions to control these diseases and thus achieve target elimination of NID. Onchocerciasis, lymphatic filariasis, Chagas disease, leprosy and trachoma blindness, among others, have been eliminated in several countries and endemic areas, regardless of the level of development of the country or geographical area where they are located. The political decision reflected in adequate financial resources in the next decade will be crucial to achieving the goals of elimination of NID (regional and national).

The vectoral role of several blackfly species (Diptera: Simuliidae) in relation to human onchocerciasis in the Sierra Parima and Upper Orinoco regions of Venezuela.

PubMed

Basáñez, M G; Yarzábal, L; Takaoka, H; Suzuki, H; Noda, S; Tada, I

1988-12-01

Experimental and natural infections with Onchocerca volvulus were studied in several anthropophilic blackfly species present in the endemic area of the Upper Orinoco region of Venezuela. When fed on four different Yanomami volunteers in the Sierra Parima, the total infection rate was 31.4% for Simulium guianense in comparison with 7.5% for S. limbatum. The proportion of ingested microfilariae that entered the thorax during the first 24 hours and completed development to the infective stage was also much lower in the latter than in the former species. There was no larval development of O. volvulus in S. antillarum, but one female harboured in its head six infective larvae of a zoonotic filaria. When S. oyapokense s.l. was fed on an infected volunteer in the Upper Orinoco most flies ingested few microfilariae, and further development reached only the L1 stage. Natural infection and infectivity rates for S. guianense in two localities of the Sierra Parima were 0.2-4.0% and 1.3-10.2%, respectively, more than 50% of the L3 larvae being in the head. The corresponding data for S. oyapockense s.l. in the Upper Orinoco were 0.1-0.5%, although the only L3 larva found did not correspond to O. volvulus. It is suggested that S. guianense is the main vector of onchocerciasis in the Sierra Parima and that S. limbatum could play a secondary role. Simulium oyapockense s.l. replaces them in the Upper Orinoco and may maintain a degree of transmission, but its epidemiological importance remains to be assessed.

Onchocerciasis modulates the immune response to mycobacterial antigens

PubMed Central

Stewart, G R; Boussinesq, M; Coulson, T; Elson, L; Nutman, T; Bradley, J E

1999-01-01

Chronic helminth infection induces a type-2 cellular immune response. In contrast to this, mycobacterial infections commonly induce a type-1 immune response which is considered protective. Type-2 responses and diminished type-1 responses to mycobacteria have been previously correlated with active infection states such as pulmonary tuberculosis and lepromatous leprosy. The present study examines the immune responses of children exposed to both the helminth parasite Onchocerca volvulus and the mycobacterial infections, Mycobacterium tuberculosis and M. leprae. Proliferation of peripheral blood mononuclear cells (PBMC) and production of IL-4 in response to both helminth and mycobacterial antigen (PPD) decreased dramatically with increasing microfilarial (MF) density. Although interferon-gamma (IFN-γ) production strongly correlated with cellular proliferation, it was surprisingly not related to MF density for either antigen. IL-4 production in response to helminth antigen and PPD increased with ascending children's age. IFN-γ and cellular proliferation to PPD were not related to age, but in response to helminth antigen were significantly higher in children of age 9–12 years than children of either the younger age group (5–8 years) or the older group (13–16 years). Thus, there was a MF density-related down-regulation of cellular responsiveness and age-related skewing toward type 2 which was paralleled in response to both the helminth antigen and PPD. This parasite-induced immunomodulation of the response to mycobacteria correlates with a previous report of doubled incidence of lepromatous leprosy in onchocerciasis hyperendemic regions. Moreover, this demonstration that helminth infection in humans can modulate the immune response to a concurrent infection or immunological challenge is of critical importance to future vaccination strategies. PMID:10469056

Elimination of Onchocerciasis from Mexico

PubMed Central

Rodríguez-Pérez, Mario A.; Fernández-Santos, Nadia A.; Orozco-Algarra, María E.; Rodríguez-Atanacio, José A.; Domínguez-Vázquez, Alfredo; Rodríguez-Morales, Kristel B.; Real-Najarro, Olga; Prado-Velasco, Francisco G.; Cupp, Eddie W.; Richards, Frank O.; Hassan, Hassan K.; González-Roldán, Jesús F.; Kuri-Morales, Pablo A.; Unnasch, Thomas R.

2015-01-01

Background Mexico is one of the six countries formerly endemic for onchocerciasis in Latin America. Transmission has been interrupted in the three endemic foci of that country and mass drug distribution has ceased. Three years after mass drug distribution ended, post-treatment surveillance (PTS) surveys were undertaken which employed entomological indicators to check for transmission recrudescence. Methodology/Principal findings In-depth entomologic assessments were performed in 18 communities in the three endemic foci of Mexico. None of the 108,212 Simulium ochraceum s.l. collected from the three foci were found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in a maximum upper bound of the 95% confidence interval (95%-ULCI) of the infective rate in the vectors of 0.035/2,000 flies examined. This is an order of magnitude below the threshold of a 95%-ULCI of less than one infective fly per 2,000 flies tested, the current entomological criterion for interruption of transmission developed by the international community. The point estimate of seasonal transmission potential (STP) was zero, and the upper bound of the 95% confidence interval for the STP ranged from 1.2 to 1.7 L3/person/season in the different foci. This value is below all previous estimates for the minimum transmission potential required to maintain the parasite population. Conclusions/Significance The results from the in-depth entomological post treatment surveillance surveys strongly suggest that transmission has not resumed in the three foci of Mexico during the three years since the last distribution of ivermectin occurred; it was concluded that transmission remains undetectable without intervention, and Onchocerca volvulus has been eliminated from Mexico. PMID:26161558

Potential vectors of loiasis and other tabanids on the island of Bioko, Equatorial Guinea.

PubMed

Cheke, R A; Mas, J; Chainey, J E

2003-06-01

The biting flies Chrysops dimidiatus Wulp and C.silaceus Austen (Diptera: Tabanidae), vectors of Loa loa (Cobbold) (Nematoda: Onchocercidae) on the African mainland, were found to be widespread on the island of Bioko (Equatorial Guinea) during 1996-2001. These tabanids were particularly prevalent in the southern part of Bioko, indicating potential transmission of loiasis on the island. The only other tabanids previously recorded on Bioko, Tabanus argenteus Surcouf (from 1915) and Haematopota near heptagramma Speiser (from 1933), were also collected. The possibility of loiasis being endemic on Bioko contra-indicates ivermectin treatment of onchocerciasis cases, due to risks of adverse side-effects.

Infectious diseases in the 21st century.

PubMed

Kumate, J

1997-01-01

Infecto-contagious diseases in the twenty-first century with respect to precedent will see themselves deprived of smallpox, dracunculiasis and very probably of paralyzing poliomyelitis. Vaccination-preventable diseases, such as measles, whooping cough, diphtheria, tetanus, rabies, some forms of meningitis, yellow fever and episodes of disseminated tuberculosis will greatly diminish in their rates of morbi-lethality; the elimination of some, and the eradication of measles, are expected. Other diseases such as diarrhea (including cholera), geo-helminthiasis, some severe respiratory tract infections and the majority of vector-transmitted infectious diseases will decrease due to improvements in potable water services, drainage, sanitary food control, living quarters, and individual and community anti-vector action. Leprosy, onchocerciasis and several parasitoses will be controlled by the available antimicrobial drugs. Infectious diseases will continue to be an important health problem due to: Reduction in the immunocompetence resulting from the aging of the population, chemotherapies necessary for neoplasms, and autoimmune pathology and the survival of persons with primary immunodeficiencies; lifestyles prone to infectious pathology, such as mega-city urbanization, children in day care centers, industrialized foods, intravenous drug addiction, sexual liberation, global commerce, and tourism; antibiotic-multiresistant microbial flora; environmental disturbances as a result of global warming, deforestation, the settling of virgin areas, dams, the large-scale use of pesticides, fertilizers and antimicrobials, and natural/social disasters generators of poverty, violence and deprivation will result in emergence or re-emergence of infectious diseases already controlled in the past.

The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

PubMed

Redekop, William K; Lenk, Edeltraud J; Luyendijk, Marianne; Fitzpatrick, Christopher; Niessen, Louis; Stolk, Wilma A; Tediosi, Fabrizio; Rijnsburger, Adriana J; Bakker, Roel; Hontelez, Jan A C; Richardus, Jan H; Jacobson, Julie; de Vlas, Sake J; Severens, Johan L

2017-01-01

Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)-also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment required by governments and their development partners within all reasonable scenarios. Given the concentration of the NTDs among the poorest households, these investments represent good value for money in efforts to share the world's prosperity and reduce inequity.

The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases

PubMed Central

Luyendijk, Marianne; Fitzpatrick, Christopher; Niessen, Louis; Stolk, Wilma A.; Tediosi, Fabrizio; Rijnsburger, Adriana J.; Bakker, Roel; Hontelez, Jan A. C.; Richardus, Jan H.; Jacobson, Julie; de Vlas, Sake J.; Severens, Johan L.

2017-01-01

Background Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)—also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Methods Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. Results The economic benefit from productivity gain was estimated to be I$251 billion in 2011–2020 and I$313 billion in 2021–2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. Conclusion Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment required by governments and their development partners within all reasonable scenarios. Given the concentration of the NTDs among the poorest households, these investments represent good value for money in efforts to share the world’s prosperity and reduce inequity. PMID:28103243

A new simple technique for rearing F1 progeny from females of the Simulium damnosum Theobald complex.

PubMed

Raybould, J N; Barro, T; Sawadogo, R; Mordzifa, F

1982-06-01

Laboratory rearing of Simulium damnosum complex species enables female adults to be indirectly identified from their larval progeny. A simple, readily transportable rearing apparatus was developed for investigations by the Onchocerciasis Control programme by using unbreakable, easily packed and reassembled parts and by feeding the larvae at least partly with living green algae (Chlorophyceae) cultured in the laboratory. Although the larvae are sensitive to excess nitrogen compounds, the use of algae and a large volume of water obviated the need for a separate purification system in which water was circulated by an A/C electrical centrifugal pump between a container and an inclined trough in which most of the larvae developed. The rate of development was rapid giving rise to full size larvae (suitable for cytotaxonomic determination), pupae and adults. The adults were attracted into a collecting device by light. Developments to protect the larvae during electrical power failures included a slow-drying wooden rearing trough and an automatic switch to an alternative D/C power supply and pump. This technique has been in general use in O.C.P. laboratories in Benin, Ghana, Ivory Coast and Upper Volta and many thousands of larvae have been reared.

The Effect of Oral Anthelmintics on the Survivorship and Re-feeding Frequency of Anthropophilic Mosquito Disease Vectors

PubMed Central

Kobylinski, Kevin C.; Deus, Kelsey M.; Butters, Matt T.; Hongyu, Tan; Gray, Meg; Silva, Ines Marques da; Sylla, Massamba; Foy, Brian D.

2010-01-01

In the Tropics, there is substantial temporal and spatial overlap of diseases propagated by anthropophilic mosquito vectors (such as malaria and dengue) and human helminth diseases (such as onchocerciasis and lymphatic filariasis) that are treated though mass drug administrations (MDA). This overlap will result in mosquito vectors imbibing significant quantities of these drugs when they blood feed on humans. Since many anthelmintic drugs have broad anti-invertebrate effects, the possibility of combined helminth control and mosquito-borne disease control through MDA is apparent. It has been previously shown that ivermectin can reduce mosquito survivorship when administered in a blood meal, but more detailed examinations are needed if MDA is to ever be developed into a tool for malaria or dengue control. We examined concentrations of drugs that follow human pharmacokinetics after MDA and that matched with mosquito feeding times, for effects against the anthropophilic mosquito vectors Anopheles gambiae s.s. and Aedes aegypti. Ivermectin was the only human-approved MDA drug we tested that affected mosquito survivorship, and only An. gambiae s.s. were affected at concentrations respecting human pharmacokinetics at indicated doses. Ivermectin also delayed An. gambiae s.s. re-feeding frequency and defecation rates, and two successive ivermectin-spiked blood meals following human pharmacokinetic concentrations compounded mortality effects compared to controls. These findings suggest that ivermectin MDA in Africa may be used to decrease malaria transmission if MDAs were administered more frequently. Such a strategy would broaden the current scope of polyparasitism control already afforded by MDAs, and which is needed in many African villages simultaneously burdened by many parasitic diseases. PMID:20540931

Control of neglected tropical diseases needs a long-term commitment.

PubMed

Zhang, Yaobi; MacArthur, Chad; Mubila, Likezo; Baker, Shawn

2010-10-29

Neglected tropical diseases are widespread, particularly in sub-Saharan Africa, affecting over 2 billion individuals. Control of these diseases has gathered pace in recent years, with increased levels of funding from a number of governmental or non-governmental donors. Focus has currently been on five major 'tool-ready' neglected tropical diseases (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis and trachoma), using a package of integrated drug delivery according to the World Health Organization guidelines for preventive chemotherapy. Success in controlling these neglected tropical diseases has been achieved in a number of countries in recent history. Experience from these successes suggests that long-term sustainable control of these diseases requires: (1) a long-term commitment from a wider range of donors and from governments of endemic countries; (2) close partnerships of donors, World Health Organization, pharmaceutical industries, governments of endemic countries, communities, and non-governmental developmental organisations; (3) concerted action from more donor countries to provide the necessary funds, and from the endemic countries to work together to prevent cross-border disease transmission; (4) comprehensive control measures for certain diseases; and (5) strengthened primary healthcare systems as platforms for the national control programmes and capacity building through implementation of the programmes. The current level of funding for the control of neglected tropical diseases has never been seen before, but it is still not enough to scale up to the 2 billion people in all endemic countries. While more donors are sought, the stakeholders must work in a coordinated and harmonised way to identify the priority areas and the best delivery approaches to use the current funds to the maximum effect. Case management and other necessary control measures should be supported through the current major funding streams in order to achieve the objectives of the control of these diseases. For a long-term and sustainable effort, control of neglected tropical diseases should also be integrated into national primary healthcare systems.

Other vector-borne parasitic diseases: animal helminthiases, bovine besnoitiosis and malaria.

PubMed

Duvallet, G; Boireau, P

2015-08-01

The parasitic diseases discussed elsewhere in this issue of the Scientific and Technical Review are not the only ones to make use of biological vectors (such as mosquitoes or ticks) or mechanical vectors (such as horse flies or Stomoxys flies). The authors discuss two major groups of vector-borne parasitic diseases: firstly, helminthiasis, along with animal filariasis and onchocerciasis, which are parasitic diseases that often take a heavytoll on artiodactylsthroughoutthe world; secondly, parasitic diseases caused by vector-borne protists, foremost of which is bovine besnoitiosis (or anasarca of cattle), which has recently spread through Europe by a dual mode of transmission (direct and by vector). Other protists, such as Plasmodium and Hepatozoon, are also described briefly.

Contribution of migrant coffee labourers infected with Onchocerca volvulus to the maintenance of the microfilarial reservoir in an ivermectin-treated area of Mexico

PubMed Central

Rodríguez-Pérez, Mario A; Cabrera, Aldo Segura; Ortega, Cristian Lizarazo; Basáñez, María-Gloria; Davies, John B

2007-01-01

Background Since 1991, in Mexico, ivermectin has been administered twice a year to all residents in the onchocerciasis endemic foci which are mainly located in the coffee growing areas. However, the presence of a potentially infected itinerant seasonal labour force which is not treated regularly could jeopardise the attainment of the 85% coverage which is the present target for elimination of the disease. Methods The prevalence and intensity of Onchocerca volvulus microfilariae (mf), as well as their transmission from humans to vectors, were assessed during the coffee planting-clearing and harvesting seasons of 1997–1998, and 1998–1999 in two localities (I and II) of Southern Chiapas, Mexico, which regularly receive an influx of untreated migrant coffee labourers. Results Localities I and II had, respectively, an average of 391 (± 32) and 358 (± 14) resident inhabitants, and 70 (± 52) and 498 (± 289) temporary labourers. The ratio of migrants to residents ranged from 0.1:1 in locality I to 2.4:1 in locality II. The proportion of infected Simulium ochraceum s.l. parous flies was significantly lower in locality I than in locality II, and significantly higher during the stay of the migrants than before their arrival or after their departure. Parity and infection were higher in May-July than in November-February (in contrast with the latter being typically considered as the peak onchocerciasis transmission season by S. ochraceum s.l.). Conclusion The presence of significant numbers of untreated and potentially infected migrants may contribute to ongoing transmission, and their incorporation into ivermectin programmes should be beneficial for the attainment of the elimination goals of the regional initiative. However, the possibility that the results also reflect transmission patterns for the area cannot be excluded and these should be analyzed further. PMID:18088423

A Research Agenda for Helminth Diseases of Humans: The Problem of Helminthiases

PubMed Central

Lustigman, Sara; Prichard, Roger K.; Gazzinelli, Andrea; Grant, Warwick N.; Boatin, Boakye A.; McCarthy, James S.; Basáñez, María-Gloria

2012-01-01

A disproportionate burden of helminthiases in human populations occurs in marginalised, low-income, and resource-constrained regions of the world, with over 1 billion people in developing areas of sub-Saharan Africa, Asia, and the Americas infected with one or more helminth species. The morbidity caused by such infections imposes a substantial burden of disease, contributing to a vicious circle of infection, poverty, decreased productivity, and inadequate socioeconomic development. Furthermore, helminth infection accentuates the morbidity of malaria and HIV/AIDS, and impairs vaccine efficacy. Polyparasitism is the norm in these populations, and infections tend to be persistent. Hence, there is a great need to reduce morbidity caused by helminth infections. However, major deficiencies exist in diagnostics and interventions, including vector control, drugs, and vaccines. Overcoming these deficiencies is hampered by major gaps in knowledge of helminth biology and transmission dynamics, platforms from which to help develop such tools. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, we provide an overview of the forces driving the persistence of helminthiases as a public health problem despite the many control initiatives that have been put in place; identify the main obstacles that impede progress towards their control and elimination; and discuss recent advances, opportunities, and challenges for the understanding of the biology, epidemiology, and control of these infections. The helminth infections that will be discussed include: onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, food-borne trematodiases, and taeniasis/cysticercosis. PMID:22545164

Distribution of larval and pupal stages of Simulium (Diptera: Simuliidae) flies in the Nilgiris hills of Tamil Nadu.

PubMed

Soundararajan, C; Nagarajan, K; Arul Prakash, M

2017-09-01

Endemicity of onchocerciasis (river blindness) in humans is linked to the location of Simulium spp. (black fly). The distribution of immature stages of Simulium in Sholur, Pykara, Gudalur, Coonoor and Kotagiri streams of the Nilgiris hills of Tamil Nadu was investigated during the months of May and July 2012. Out of these five streams, only Sholur was infested with larval and pupal stages of Simulium spp. Out of six plants collected from various water bodies, larval and pupal stages were found on the leaves and stems of an aquatic plant Nasturtium officinale and on the roots and leaves of Pennisetum glandulosum. The stages of Simulium were observed only during the summer month of May.

The eradication of Simulium neavei from Kenya

PubMed Central

McMahon, J. P.; Highton, R. B.; Goiny, H.

1958-01-01

S. neavei, the vector of onchocerciasis, has been virtually eradicated from Kenya by larviciding measures in which DDT was used. Only a very small area remains infested and this is in the course of being treated by the Uganda medical authorities as it is part of a much larger focus occurring in that country. An account is given of the various surveys which have been carried out during the last ten years in Nyanza Province, involving 15 000 square miles (about 40 000 km2), and survey techniques are described. An account is given of the eradication measures carried out in North and South Nyanza, and techniques in connexion with dosing and checking operations are described. Costs for both surveys and eradication schemes are given, and minimum requirements for transport are indicated. PMID:13585062

Land-use change and infectious disease in West Africa

NASA Astrophysics Data System (ADS)

Thomson, M. C.; Ericksen, P. J.; Mohamed, A. Ben; Connor, S. J.

Land-use change has been associated with changes in the dynamics of infectious disease in West Africa. Here we describe the complex interactions of land-use change with three diseases (both vector- and non-vector-borne) of considerable public health significance in this region, namely, malaria and irrigation; epidemic meningitis and land degradation; onchocerciasis and deforestation. We highlight the confounding effect of climate variability, which acts as a driver of both land-use change and human health. We conclude, as have others, that the scale of observation always matters, and complex and dynamic feedbacks among social-ecological systems are not easily teased apart. We suggest that in order to establish the causal chain of interactions between land-use change and human health outcomes two approaches are necessary. The first is to have a thorough understanding of the aetiology of disease and the specific mechanisms by which land-use and climate variability affect the transmission of pathogens. This is achieved by focused, detailed studies encompassing a wide range of potential drivers, which are inevitably small scale and often cover short time periods. The second consists of large-scale studies of statistical associations between transmission indices or health outcomes and environmental variables stratified by known ecological or socio-economic confounders, and sufficient in size to overcome local biases in results. Such research activities need to be designed to inform each other if we are to develop predictive models for monitoring these diseases and to develop integrated programs for human health and sustainable land use.

Concerted Efforts to Control or Eliminate Neglected Tropical Diseases: How Much Health Will Be Gained?

PubMed Central

Hontelez, Jan A. C.; Bakker, Roel; Blok, David J.; Cai, Rui; Houweling, Tanja A. J.; Kulik, Margarete C.; Lenk, Edeltraud J.; Luyendijk, Marianne; Matthijsse, Suzette M.; Redekop, William K.; Wagenaar, Inge; Jacobson, Julie; Nagelkerke, Nico J. D.; Richardus, Jan H.

2016-01-01

Background The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas’ disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). Methods The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. Principle Findings/Conclusions Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011–2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts. PMID:26890362

Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa

PubMed Central

Büttner, Dietrich W; Wanji, Samuel; Bazzocchi, Chiara; Bain, Odile; Fischer, Peter

2003-01-01

Background Many filarial nematodes harbour Wolbachia endobacteria. These endobacteria are transmitted vertically from one generation to the next. In several filarial species that have been studied to date they are obligatory symbionts of their hosts. Elimination of the endobacteria by antibiotics interrupts the embryogenesis and hence the production of microfilariae. The medical implication of this being that the use of doxycycline for the treatment of human onchocerciasis and bancroftian filariasis leads to elimination of the Wolbachia and hence sterilisation of the female worms. Wolbachia play a role in the immunopathology of patients and may contribute to side effects seen after antifilarial chemotherapy. In several studies Wolbachia were not observed in Loa loa. Since these results have been doubted, and because of the medical significance, several independent methods were applied to search for Wolbachia in L. loa. Methods Loa loa and Onchocerca volvulus were studied by electron microscopy, histology with silver staining, and immunohistology using antibodies against WSP, Wolbachia aspartate aminotransferase, and heat shock protein 60. The results achieved with L. loa and O. volvulus were compared. Searching for Wolbachia, genes were amplified by PCR coding for the bacterial 16S rDNA, the FTSZ cell division protein, and WSP. Results No Wolbachia endobacteria were discovered by immunohistology in 13 male and 14 female L. loa worms and in numerous L. loa microfilariae. In contrast, endobacteria were found in large numbers in O. volvulus and 14 other filaria species. No intracellular bacteria were seen in electron micrographs of oocytes and young morulae of L. loa in contrast to O. volvulus. In agreement with these results, Wolbachia DNA was not detected by PCR in three male and six female L. loa worms and in two microfilariae samples of L. loa. Conclusions Loa loa do not harbour obligatory symbiotic Wolbachia endobacteria in essential numbers to enable their efficient vertical transmission or to play a role in production of microfilariae. Exclusively, the filariae cause the immunopathology of loiasis is patients and the adverse side effects after antifilarial chemotherapy. Doxycycline cannot be used to cure loiais but it probably does not represent a risk for L. loa patients when administered to patients with co-infections of onchocerciasis. PMID:12801420

Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy

PubMed Central

Albonico, M.; Levecke, B.; LoVerde, P.T.; Montresor, A.; Prichard, R.; Vercruysse, J.; Webster, J.P.

2017-01-01

In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. PMID:27842865

A Research Agenda for Helminth Diseases of Humans: Intervention for Control and Elimination

PubMed Central

Prichard, Roger K.; Basáñez, María-Gloria; Boatin, Boakye A.; McCarthy, James S.; García, Héctor H.; Yang, Guo-Jing; Sripa, Banchob; Lustigman, Sara

2012-01-01

Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. A summary of current helminth control initiatives is presented and available tools are described. Most of these programmes are highly dependent on mass drug administration (MDA) of anthelmintic drugs (donated or available at low cost) and require annual or biannual treatment of large numbers of at-risk populations, over prolonged periods of time. The continuation of prolonged MDA with a limited number of anthelmintics greatly increases the probability that drug resistance will develop, which would raise serious problems for continuation of control and the achievement of elimination. Most initiatives have focussed on a single type of helminth infection, but recognition of co-endemicity and polyparasitism is leading to more integration of control. An understanding of the implications of control integration for implementation, treatment coverage, combination of pharmaceuticals, and monitoring is needed. To achieve the goals of morbidity reduction or elimination of infection, novel tools need to be developed, including more efficacious drugs, vaccines, and/or antivectorial agents, new diagnostics for infection and assessment of drug efficacy, and markers for possible anthelmintic resistance. In addition, there is a need for the development of new formulations of some existing anthelmintics (e.g., paediatric formulations). To achieve ultimate elimination of helminth parasites, treatments for the above mentioned helminthiases, and for taeniasis and food-borne trematodiases, will need to be integrated with monitoring, education, sanitation, access to health services, and where appropriate, vector control or reduction of the parasite reservoir in alternative hosts. Based on an analysis of current knowledge gaps and identification of priorities, a research and development agenda for intervention tools considered necessary for control and elimination of human helminthiases is presented, and the challenges to be confronted are discussed. PMID:22545163

Commentary: restarting NTD programme activities after the Ebola outbreak in Liberia.

PubMed

Thomas, Brent C; Kollie, Karsor; Koudou, Benjamin; Mackenzie, Charles

2017-05-01

It is widely known that the recent Ebola Virus Disease (EVD) in West Africa caused a serious disruption to the national health system, with many of ongoing disease focused programmes, such as mass drug administration (MDA) for onchocerciasis (ONC), lymphatic filariasis (LF) and schistosomiasis (SCH), being suspended or scaled-down. As these MDA programmes attempt to restart post-EVD it is important to understand the challenges that may be encountered. This commentary addresses the opinions of the major health sectors involved, as well as those of community members, regarding logistic needs and challenges faced as these important public health programmes consider restarting. There appears to be a strong desire by the communities to resume NTD programme activities, although it is clear that some important challenges remain, the most prominent being those resulting from the severe loss of trained staff.

Global data on blindness.

PubMed Central

Thylefors, B.; Négrel, A. D.; Pararajasegaram, R.; Dadzie, K. Y.

1995-01-01

Globally, it is estimated that there are 38 million persons who are blind. Moreover, a further 110 million people have low vision and are at great risk of becoming blind. The main causes of blindness and low vision are cataract, trachoma, glaucoma, onchocerciasis, and xerophthalmia; however, insufficient data on blindness from causes such as diabetic retinopathy and age-related macular degeneration preclude specific estimations of their global prevalence. The age-specific prevalences of the major causes of blindness that are related to age indicate that the trend will be for an increase in such blindness over the decades to come, unless energetic efforts are made to tackle these problems. More data collected through standardized methodologies, using internationally accepted (ICD-10) definitions, are needed. Data on the incidence of blindness due to common causes would be useful for calculating future trends more precisely. PMID:7704921

Reproductive Status of Onchocerca volvulus after Ivermectin Treatment in an Ivermectin-Naïve and a Frequently Treated Population from Cameroon

PubMed Central

Bopda, Jean; Kengne-Ouafo, Jonas A.; Njiokou, Flobert; Prichard, Roger K.; Wanji, Samuel; Kamgno, Joseph; Boussinesq, Michel

2014-01-01

Background For two decades, onchocerciasis control has been based on mass treatment with ivermectin (IVM), repeated annually or six-monthly. This drug kills Onchocerca volvulus microfilariae (mf) present in the skin and the eyes (microfilaricidal effect) and prevents for 3–4 months the release of new mf by adult female worms (embryostatic effect). In some Ghanaian communities, the long-term use of IVM was associated with a more rapid than expected skin repopulation by mf after treatment. Here, we assessed whether the embryostatic effect of IVM on O. volvulus has been altered following frequent treatment in Cameroonian patients. Methodology Onchocercal nodules were surgically removed just before (D0) and 80 days (D80) after a standard dose of IVM in two cohorts with different treatment histories: a group who had received repeated doses of IVM over 13 years, and a control group with no history of large-scale treatments. Excised nodules were digested with collagenase to isolate adult worms. Embryograms were prepared with females for the evaluation of their reproductive capacities. Principal Findings Oocyte production was not affected by IVM. The mean number of intermediate embryos (morulae and coiled mf) decreased similarly in the two groups between D0 and D80. In contrast, an accumulation of stretched mf, either viable or degenerating, was observed at D80. However, it was observed that the increase in number of degenerating mf between D0 and D80 was much lower in the frequently treated group than in the control one (Incidence Rate Ratio: 0.25; 95% CI: 0.10–0.63; p = 0.003), which may indicate a reduced sequestration of mf in the worms from the frequently treated group. Conclusion/Significance IVM still had an embryostatic effect on O. volvulus, but the effect was reduced in the frequently treated cohort compared with the control population. PMID:24762816

Changes in the use profile of Mectizan: 1987-1997.

PubMed

Brown, K R

1998-04-01

The usually conservative approach of Merck & Co. to drug development became even more so in the Mectizan (ivermectin, MSD) programme because of adverse experiences following 'extra-label' use in Collie dogs and the discovery of a low threshold for acute neurotoxicity in CF-1 mice. Although a very cautious approach and rapid development programme ensued, Merck remained conservative and excluded children under the age of 5 years, pregnant women, and mother who were nursing children under the age of 3 months from treatment. A subsequent, more relaxed set of standards was based on vast human clinical experience, inadvertent use in hundreds of pregnant women without ill-effect, and new laboratory information indicating that the presence of a protective blood-brain barrier protein component (P-glycoprotein) helped to stop Mectizan from crossing the placenta and from crossing the blood-brain barrier in most animal species, including humans. This has allowed more groups to be included in Mectizan treatments: pregnant women living in areas where the risk of loss of sight because of onchocerciasis is very high; and women who are nursing children as young as 1 week of age. Mass distribution of the drug continues to be largely under community control and the likelihood of serious adverse experiences related to finding a human population with unusually low levels of P-glycoprotein (or no P-glycoprotein) seems remote.

Looking forward to 20/20: a focus on the epidemiology of eye diseases.

PubMed

West, S K

2000-01-01

The encouraging scenario of international efforts to eliminate preventable and avoidable blindness is the legacy of public health ophthalmology in the 20th century. With active programs currently in place or beginning for the major cause of blindness in childhood and two of the leading infectious causes of blindness, it is natural that research in eye disease will shift even more heavily toward the leading causes of blindness in the older ages. The age-related eye diseases will rapidly become the most common causes of blindness and visual loss and, with the exception of cataract, are the more difficult to identify, diagnose, and treat. The human misery and social cost of blindness, especially in the countries that can ill afford it, are profound. To combat this problem, epidemiologic research in ophthalmology should look toward the following major areas: 1. the identification and testing of better screening modalities to determine early changes possibly amenable to preventive strategies. This includes detection of vitamin A deficiency as well. 2. the creation of uniform definitions for diseases, particularly glaucoma and early AMD, which have relevance for epidemiologic research into risk factors. 3. increased multidisciplinary research, working with investigators skilled in molecular genetics, biologic markers for age-related diseases, and those interested in new imaging and vision-testing techniques. 4. ongoing work in clinical trials of new approaches to prevent or delay the onset of vision loss from eye disease, including future vaccines for chlamydia and onchocerciasis. The major public health issue of blindness prevention will not disappear in the next century but only shift emphasis to different causes if the current programs achieve the success that is hoped. Future epidemiologic research will continue to require a concerted, sustained, and multidisciplinary effort in order to contribute to the vision research agenda in the next century.

Perception of blindness and blinding eye conditions in rural communities.

PubMed Central

Ashaye, Adeyinka; Ajuwon, Ademola Johnson; Adeoti, Caroline

2006-01-01

PURPOSE: The purpose of this qualitative study was to explore the causes and management of blindness and blinding eye conditions as perceived by rural dwellers of two Yoruba communities in Oyo State, Nigeria. METHODS: Four focus group discussions were conducted among residents of Iddo and Isale Oyo, two rural Yoruba communities in Oyo State, Nigeria. Participants consisted of sighted, those who were partially or totally blind and community leaders. Ten patent medicine sellers and 12 traditional healers were also interviewed on their perception of the causes and management of blindness in their communities. FINDINGS: Blindness was perceived as an increasing problem among the communities. Multiple factors were perceived to cause blindness, including germs, onchocerciasis and supernatural forces. Traditional healers believed that blindness could be cured, with many claiming that they had previously cured blindness in the past. However, all agreed that patience was an important requirement for the cure of blindness. The patent medicine sellers' reports were similar to those of the traditional healers. The barriers to use of orthodox medicine were mainly fear, misconception and perceived high costs of care. There was a consensus of opinion among group discussants and informants that there are severe social and economic consequences of blindness, including not been able to see and assess the quality of what the sufferer eats, perpetual sadness, loss of sleep and dependence on other persons for daily activities. CONCLUSION: Local beliefs associated with causation, symptoms and management of blindness and blinding eye conditions among rural Yoruba communities identified have provided a bridge for understanding local perspectives and basis for implementing appropriate primary eye care programs. PMID:16775910

Perception of blindness and blinding eye conditions in rural communities.

PubMed

Ashaye, Adeyinka; Ajuwon, Ademola Johnson; Adeoti, Caroline

2006-06-01

The purpose of this qualitative study was to explore the causes and management of blindness and blinding eye conditions as perceived by rural dwellers of two Yoruba communities in Oyo State, Nigeria. Four focus group discussions were conducted among residents of Iddo and Isale Oyo, two rural Yoruba communities in Oyo State, Nigeria. Participants consisted of sighted, those who were partially or totally blind and community leaders. Ten patent medicine sellers and 12 traditional healers were also interviewed on their perception of the causes and management of blindness in their communities. Blindness was perceived as an increasing problem among the communities. Multiple factors were perceived to cause blindness, including germs, onchocerciasis and supernatural forces. Traditional healers believed that blindness could be cured, with many claiming that they had previously cured blindness in the past. However, all agreed that patience was an important requirement for the cure of blindness. The patent medicine sellers' reports were similar to those of the traditional healers. The barriers to use of orthodox medicine were mainly fear, misconception and perceived high costs of care. There was a consensus of opinion among group discussants and informants that there are severe social and economic consequences of blindness, including not been able to see and assess the quality of what the sufferer eats, perpetual sadness, loss of sleep and dependence on other persons for daily activities. Local beliefs associated with causation, symptoms and management of blindness and blinding eye conditions among rural Yoruba communities identified have provided a bridge for understanding local perspectives and basis for implementing appropriate primary eye care programs.

Monitoring the efficacy of drugs for neglected tropical diseases controlled by preventive chemotherapy.

PubMed

Albonico, M; Levecke, B; LoVerde, P T; Montresor, A; Prichard, R; Vercruysse, J; Webster, J P

2015-12-01

In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel. Copyright © 2015 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Natural Products as a Source for Treating Neglected Parasitic Diseases

PubMed Central

Ndjonka, Dieudonné; Rapado, Ludmila Nakamura; Silber, Ariel M.; Liebau, Eva; Wrenger, Carsten

2013-01-01

Infectious diseases caused by parasites are a major threat for the entire mankind, especially in the tropics. More than 1 billion people world-wide are directly exposed to tropical parasites such as the causative agents of trypanosomiasis, leishmaniasis, schistosomiasis, lymphatic filariasis and onchocerciasis, which represent a major health problem, particularly in impecunious areas. Unlike most antibiotics, there is no “general” antiparasitic drug available. Here, the selection of antiparasitic drugs varies between different organisms. Some of the currently available drugs are chemically de novo synthesized, however, the majority of drugs are derived from natural sources such as plants which have subsequently been chemically modified to warrant higher potency against these human pathogens. In this review article we will provide an overview of the current status of plant derived pharmaceuticals and their chemical modifications to target parasite-specific peculiarities in order to interfere with their proliferation in the human host. PMID:23389040

Long-term treatment of onchocerciasis patients from the Liberian rain-forest with low doses of diethylcarbamazine citrate after complete nodulectomy.

PubMed

Albiez, E J

1983-12-01

60 completely nodulectomized volunteers from the Liberian rain-forest were given an initial treatment with diethylcarbamazine citrate (DEC-C) for one week with gradually increasing doses up to a total of 1.1 g per patient. A long-term treatment followed with 50 mg DEC-C per week for 12 months. Immediately after the initial treatment the mean microfilarial density decreased to 4% to 6% of the pre-treatment level. After one year the microfilarial density had again increased to 12% to 29% of the pre-treatment level. Although the intake of the weekly 50 mg DEC-C was in no case regular, the microfilarial densities could be kept at a low level throughout the trial. However, even with the combined treatment--preceding nodulectomy and long-term trial with DEC-C--it was not possible to get the patients free from microfilariae.

Corneal blindness: a global perspective.

PubMed Central

Whitcher, J. P.; Srinivasan, M.; Upadhyay, M. P.

2001-01-01

Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance. The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseses that cause corneal scarring, which ultimately leads to functional blindness. In addition, the prevalence of corneal disease varies from country to country and even from one population to another. While cataract is responsible for nearly 20 million of the 45 million blind people in the world, the next major cause is trachoma which blinds 4.9 million individuals, mainly as a result of corneal scarring and vascularization. Ocular trauma and corneal ulceration are significant causes of corneal blindness that are often underreported but may be responsible for 1.5-2.0 million new cases of monocular blindness every year. Causes of childhood blindness (about 1.5 million worldwide with 5 million visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia neonatorum, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis. Even though the control of onchocerciasis and leprosy are public health success stories, these diseases are still significant causes of blindness--affecting a quarter of a million individuals each. Traditional eye medicines have also been implicated as a major risk factor in the current epidemic of corneal ulceration in developing countries. Because of the difficulty of treating corneal blindness once it has occurred, public health prevention programmes are the most cost-effective means of decreasing the global burden of corneal blindness. PMID:11285665

Triple Co-Administration of Ivermectin, Albendazole and Praziquantel in Zanzibar: A Safety Study

PubMed Central

Mohammed, Khalfan A.; Haji, Hamad J.; Gabrielli, Albis-Francesco; Mubila, Likezo; Biswas, Gautam; Chitsulo, Lester; Bradley, Mark H.; Engels, Dirk; Savioli, Lorenzo; Molyneux, David H.

2008-01-01

Background Public health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention. Methodology/Principal Findings Ivermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events. Conclusions/Significance Our data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs. PMID:18235853

Lack of Active Onchocerca volvulus Transmission in the Northern Chiapas Focus of Mexico

PubMed Central

Rodríguez-Pérez, Mario A.; Unnasch, Thomas R.; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L.; Richards, Frank; Peña-Flores, Graciela P.; Orozco-Algarra, María Eugenia; Prado-Velasco, Gibert

2010-01-01

The northern Chiapas onchocerciasis focus has undergone 11 years of ivermectin mass treatment. No evidence of microfilariae in the cornea and/or anterior chamber of the eye or in skin snips was seen in residents examined in 2006 in two sentinel communities (upper limit of the 95% confidence interval [UL 95% CI] = 0.5% and 0.3%, respectively). In children 10 and under, 0 of 305 were found to harbor antibodies to Ov16, a marker of parasite exposure; 0 of 4,400 Simulium ochraceum s.l. collected in 2005 contained parasite DNA, giving an UL 95% CI for the infective rate of 0.9/2,000, and an UL 95% CI of the seasonal transmission potential of 1.2 L3/person. These data, assumed to be representative of the focus as a whole, suggest that there is no ongoing transmission of Onchocerca volvulus in the northern Chiapas focus. Community-wide treatments with ivermectin were halted in 2008, and a post-treatment surveillance phase was initiated. PMID:20595471

History of Human Parasitology

PubMed Central

Cox, F. E. G.

2002-01-01

Humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa, some derived from our primate ancestors and some acquired from the animals we have domesticated or come in contact with during our relatively short history on Earth. Our knowledge of parasitic infections extends into antiquity, and descriptions of parasites and parasitic infections are found in the earliest writings and have been confirmed by the finding of parasites in archaeological material. The systematic study of parasites began with the rejection of the theory of spontaneous generation and the promulgation of the germ theory. Thereafter, the history of human parasitology proceeded along two lines, the discovery of a parasite and its subsequent association with disease and the recognition of a disease and the subsequent discovery that it was caused by a parasite. This review is concerned with the major helminth and protozoan infections of humans: ascariasis, trichinosis, strongyloidiasis, dracunculiasis, lymphatic filariasis, loasis, onchocerciasis, schistosomiasis, cestodiasis, paragonimiasis, clonorchiasis, opisthorchiasis, amoebiasis, giardiasis, African trypanosomiasis, South American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, cryptosporidiosis, cyclosporiasis, and microsporidiosis. PMID:12364371

History of human parasitology.

PubMed

Cox, F E G

2002-10-01

Humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa, some derived from our primate ancestors and some acquired from the animals we have domesticated or come in contact with during our relatively short history on Earth. Our knowledge of parasitic infections extends into antiquity, and descriptions of parasites and parasitic infections are found in the earliest writings and have been confirmed by the finding of parasites in archaeological material. The systematic study of parasites began with the rejection of the theory of spontaneous generation and the promulgation of the germ theory. Thereafter, the history of human parasitology proceeded along two lines, the discovery of a parasite and its subsequent association with disease and the recognition of a disease and the subsequent discovery that it was caused by a parasite. This review is concerned with the major helminth and protozoan infections of humans: ascariasis, trichinosis, strongyloidiasis, dracunculiasis, lymphatic filariasis, loasis, onchocerciasis, schistosomiasis, cestodiasis, paragonimiasis, clonorchiasis, opisthorchiasis, amoebiasis, giardiasis, African trypanosomiasis, South American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, cryptosporidiosis, cyclosporiasis, and microsporidiosis.

Mucocutaneous manifestations of helminth infections: Trematodes and cestodes.

PubMed

Lupi, Omar; Downing, Christopher; Lee, Michael; Bravo, Francisco; Giglio, Patricia; Woc-Colburn, Laila; Tyring, Stephen K

2015-12-01

In the 21st century, despite increased international travel for vacation, work, and medical missions and immigration into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. It has been estimated that 20% to 70% of international travelers suffer from some travel-related health problem. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on cutaneous diseases caused by helminth infections. Part I of the review focused on nematode infections; part II will focus on trematode and cestode infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle.

PubMed

Armstrong, Stuart D; Xia, Dong; Bah, Germanus S; Krishna, Ritesh; Ngangyung, Henrietta F; LaCourse, E James; McSorley, Henry J; Kengne-Ouafo, Jonas A; Chounna-Ndongmo, Patrick W; Wanji, Samuel; Enyong, Peter A; Taylor, David W; Blaxter, Mark L; Wastling, Jonathan M; Tanya, Vincent N; Makepeace, Benjamin L

2016-08-01

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilize the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin domain family, which was originally described from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp. proteome across the lifecycle highlights its profound complexity and emphasizes the extremely close relationship between O. ochengi and O. volvulus The insights presented here provide new candidates for vaccine development, drug targeting and diagnostic biomarkers. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Between-Country Inequalities in the Neglected Tropical Disease Burden in 1990 and 2010, with Projections for 2020.

PubMed

Stolk, Wilma A; Kulik, Margarete C; le Rutte, Epke A; Jacobson, Julie; Richardus, Jan Hendrik; de Vlas, Sake J; Houweling, Tanja A J

2016-05-01

The World Health Organization (WHO) has set ambitious time-bound targets for the control and elimination of neglected tropical diseases (NTDs). Investing in NTDs is not only seen as good value for money, but is also advocated as a pro-poor policy since it would improve population health in the poorest populations. We studied the extent to which the disease burden from nine NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, trachoma, Chagas disease, human African trypanosomiasis, leprosy, visceral leishmaniasis) was concentrated in the poorest countries in 1990 and 2010, and how this would change by 2020 in case the WHO targets are met. Our analysis was based on 1990 and 2010 data from the Global Burden of Disease (GBD) 2010 study and on projections of the 2020 burden. Low and lower-middle income countries together accounted for 69% and 81% of the global burden in 1990 and 2010 respectively. Only the soil-transmitted helminths and Chagas disease caused a considerable burden in upper-middle income countries. The global burden from these NTDs declined by 27% between 1990 and 2010, but reduction largely came to the benefit of upper-middle income countries. Achieving the WHO targets would lead to a further 55% reduction in the global burden between 2010 and 2020 in each country income group, and 81% of the global reduction would occur in low and lower-middle income countries. The GBD 2010 data show the burden of the nine selected NTDs in DALYs is strongly concentrated in low and lower-middle income countries, which implies that the beneficial impact of NTD control eventually also largely comes to the benefit of these same countries. While the nine NTDs became increasingly concentrated in developing countries in the 1990-2010 period, this trend would be rectified if the WHO targets were met, supporting the pro-poor designation.

Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity

PubMed Central

Endara, P; Vaca, M; Chico, M E; Erazo, S; Oviedo, G; Quinzo, I; Rodriguez, A; Lovato, R; Moncayo, A-L; Barreto, M L; Rodrigues, L C; Cooper, P J

2010-01-01

Background The low prevalence of allergic disease in the rural tropics has been attributed to the protective effects of chronic helminth infections. There is concern that treatment-based control programmes for these parasites may lead to an increase in the prevalence of allergic diseases. Objective We measured the impact of 15–17 years of anthelmintic treatment with ivermectin on the prevalence of allergen skin test reactivity and allergic symptoms in school-age children. Methods The prevalence of allergen skin test reactivity, exercise-induced bronchospasm and allergic symptoms was compared between school-age children living in communities that had received community-based treatments with ivermectin (for onchocerciasis control) for a period of 15–17 years with those living in geographically adjacent communities that had received no ivermectin. Results The prevalence of allergen skin test reactivity was double in children living in treated communities compared with those in untreated communities (16.7% vs. 8.7%, adjusted OR 2.10, 95% CI 1.50–2.94, P<0.0001), and the effect was mediated partly by a reduced prevalence of Trichuris trichiura among treated children. Ivermectin treatments were associated with an increased prevalence of recent eczema symptoms (adjusted OR 2.24, 95% CI 1.05–4.78, P=0.04) but not symptoms of asthma or rhino-conjunctivitis. The effect on eczema symptoms was not associated with reductions in geohelminth infections. Conclusion Long-term periodic treatments with ivermectin were associated with an increased prevalence of allergen skin test reactivity. There was some evidence that treatment was associated with an increased prevalence of recent eczema symptoms but not those of asthma or rhino-conjunctivitis. Cite this as: P. Endara, M. Vaca, M. E. Chico, S. Erazo, G. Oviedo, I. Quinzo, A. Rodriguez R. Lovato, A.-L. Moncayo, M. L. Barreto, L. C. Rodrigues and P. J. Cooper, Clinical & Experimental Allergy, 2010 (40) 1669–1677. PMID:21039971

Stage-specific Proteomes from Onchocerca ochengi, Sister Species of the Human River Blindness Parasite, Uncover Adaptations to a Nodular Lifestyle*

PubMed Central

Armstrong, Stuart D.; Xia, Dong; Bah, Germanus S.; Krishna, Ritesh; Ngangyung, Henrietta F.; LaCourse, E. James; McSorley, Henry J.; Kengne-Ouafo, Jonas A.; Chounna-Ndongmo, Patrick W.; Wanji, Samuel; Enyong, Peter A.; Taylor, David W.; Blaxter, Mark L.; Wastling, Jonathan M.; Tanya, Vincent N.; Makepeace, Benjamin L.

2016-01-01

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilize the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin domain family, which was originally described from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp. proteome across the lifecycle highlights its profound complexity and emphasizes the extremely close relationship between O. ochengi and O. volvulus. The insights presented here provide new candidates for vaccine development, drug targeting and diagnostic biomarkers. PMID:27226403

[Evaluation of the efficacity of coconut (Cocos nucifera), palm nut (Eleais guineensis) and gobi (Carapa procera) lotions and creams in indivirual protection against Simulium damnosum s.l. bites in Côte d'Ivoire].

PubMed

Sylla, M; Konan, L; Doannio, J M; Traoré, S

2003-05-01

With the interruption of larva treatments done by OCP as part of onchocerciasis control in West Africa, Simulium came back in abundance in forest regions and savannah fertile valleys. In addition to the severe discomfort, nuisance by Simulium is in certain cases incompatible with land use. Since ground treatment of larval breading sites using insecticides is not always possible or efficient, it is therefore a necessity to develop other methods among which individual protection against Simulium bites. The general objective of our study was to evaluate different vegetable oil compound repellent formulas against Simulium bites. Activities were carried out in savannah zone (Niakaramandougou) and in forest zone (Soubré) in Côte d'Ivoire. The methodology consisted in catching blackflies on volunteers whose legs were rubbed with a repellent. Gobi raw oil and coconut, palm nut and gobi formulas (lotions and creams) were tested. During each session, which lasted from 07:00 am to 12:00 and from 03:00 pm to 06:00 pm, one person did not apply any repellent and was used as the control person. The results of our experimentations show that for a given zone (savannah, forest), a repellent (coconut, palm nut, gobi) and a compound (shea butter, vaseline), there is no significant difference between protection rates obtained with lotions (maximum: 21 bites/person/day) and those obtained with creams (maximum: 30 bites/person/day). In other respects, the lotion of a given repellent seems to be efficient in savannah as in the forest, in protecting against Simulium bites. It is the same situation with creams. So, repellents can be an efficient solution against Simulium nuisance. However, experimentations should continue to confirm the high repellency of tested formulas, proceed to the identification of principles and evaluate the toxicity and irritant effect of repellents to be applied on the skin.

Socioeconomic Inequalities in Neglected Tropical Diseases: A Systematic Review

PubMed Central

Houweling, Tanja A. J.; Karim-Kos, Henrike E.; Kulik, Margarete C.; Stolk, Wilma A.; Haagsma, Juanita A.; Lenk, Edeltraud J.; Richardus, Jan Hendrik; de Vlas, Sake J.

2016-01-01

Background Neglected tropical diseases (NTDs) are generally assumed to be concentrated in poor populations, but evidence on this remains scattered. We describe within-country socioeconomic inequalities in nine NTDs listed in the London Declaration for intensified control and/or elimination: lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminthiasis (STH), trachoma, Chagas’ disease, human African trypanosomiasis (HAT), leprosy, and visceral leishmaniasis (VL). Methodology We conducted a systematic literature review, including publications between 2004–2013 found in Embase, Medline (OvidSP), Cochrane Central, Web of Science, Popline, Lilacs, and Scielo. We included publications in international peer-reviewed journals on studies concerning the top 20 countries in terms of the burden of the NTD under study. Principal findings We identified 5,516 publications, of which 93 met the inclusion criteria. Of these, 59 papers reported substantial and statistically significant socioeconomic inequalities in NTD distribution, with higher odds of infection or disease among poor and less-educated people compared with better-off groups. The findings were mixed in 23 studies, and 11 studies showed no substantial or statistically significant inequality. Most information was available for STH, VL, schistosomiasis, and, to a lesser extent, for trachoma. For the other NTDs, evidence on their socioeconomic distribution was scarce. The magnitude of inequality varied, but often, the odds of infection or disease were twice as high among socioeconomically disadvantaged groups compared with better-off strata. Inequalities often took the form of a gradient, with higher odds of infection or disease each step down the socioeconomic hierarchy. Notwithstanding these inequalities, the prevalence of some NTDs was sometimes also high among better-off groups in some highly endemic areas. Conclusions While recent evidence on socioeconomic inequalities is scarce for most individual NTDs, for some, there is considerable evidence of substantially higher odds of infection or disease among socioeconomically disadvantaged groups. NTD control activities as proposed in the London Declaration, when set up in a way that they reach the most in need, will benefit the poorest populations in poor countries. PMID:27171166

Experiences and perspectives of community health workers from implementing treatment for schistosomiasis using the community directed intervention strategy in an informal settlement in Kisumu City, western Kenya.

PubMed

Odhiambo, Gladys O; Musuva, Rosemary M; Odiere, Maurice R; Mwinzi, Pauline N

2016-09-15

The Community Directed Intervention (CDI) strategy has been used to conduct various health interventions in Africa, including control of Neglected Tropical Diseases (NTDs). Although the CDI approach has shown good results in the control of onchocerciasis and lymphatic filariasis with respect to treatment coverage using community drug distributors, its utility in the control of schistosomiasis among urban poor is yet to be established. Using a longitudinal qualitative study, we explored the experiences, opportunities, challenges as well as recommendations of Community Health Workers (CHWs) after participation in annual mass drug administration (MDA) activities for schistosomiasis using the CDI approach in an urban setting. Unstructured open-ended group discussions were conducted with CHWs after completion of annual MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussions, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.ti. software, and themes explored using the principle of interpretative phenomenological analysis (IPA). From the perspective of the CHWs, opportunities for implementing CDI in urban settings, included the presence of CHWs, their supervisory structures and their knowledge of intervention areas, and opportunity to integrate MDA with other health interventions. Several challenges were mentioned with regards to implementing MDA using the CDI strategy among them lack of incentives, fear of side effects, misconceptions regarding treatment and mistrust, difficulties working in unsanitary environmental conditions, insecurity, and insufficient time. A key recommendation in promoting more effective MDA using the CDI approach was allocation of more time to the exercise. Findings from this study support the feasibility of using CDI for implementing MDA for schistosomiasis in informal settlements of urban areas. Extensive community sensitization and provision of incentives may help address the aforementioned challenges associated with implementing MDA using the CDI strategy. Opportunities highlighted in this study may be of value to other programmes that may be considering the adoption of the CDI strategy for rolling out interventions in the urban setting.

Nobel prize for the artemisinin and ivermectin discoveries: a great boost towards elimination of the global infectious diseases of poverty.

PubMed

Tambo, Ernest; Khater, Emad I M; Chen, Jun-Hu; Bergquist, Robert; Zhou, Xiao-Nong

2015-12-28

The Millennium Development Goals (MDGs) made a marked transformation for neglected and vulnerable communities in the developing countries from the start, but infectious diseases of poverty (IDoPs) continue to inflict a disproportionate global public health burden with associated consequences, thereby contributing to the vicious cycle of poverty and inequity. However, the effectiveness and large-scale coverage of artemisinin combination therapy (ACT) have revolutionized malaria treatment just as the control of lymphatic filariasis (LF) and onchocerciasis have benefitted from harnessing the broad-spectrum effect of avermectin-based derivatives. The paradigm shift in therapeutic approach, effected by these two drugs and their impact on community-based interventions of parasitic diseases plaguing the endemic low- and middle-income countries (LIMCs), led to the Nobel Prize in Physiology or Medicine in 2015. However, the story would not be complete without mentioning praziquantel. The huge contribution of this drug in modernizing the control of schistosomiasis and also some intestinal helminth infections had already shifted the focus from control to potential elimination of this disease. Together, these new drugs have provided humankind with powerful new tools for the alleviation of infectious diseases that humans have lived with since time immemorial. These drugs all have broad-spectrum effects, yet they are very safe and can even be packaged together in various combinations. The strong effect on so many of the great infectious scourges in the developing countries has not only had a remarkable influence on many endemic diseases, but also contributed to improving the cost structure of healthcare. Significant benefits include improved quality of preventive and curative medicine, promotion of community-based interventions, universal health coverage and the fostering of global partnerships. The laudable progress and benefits achieved are indispensable in championing, strengthening and moving forward elimination of the IDoPs. However, there is an urgent need for further innovative, contextual and integrated approaches along with the advent of the Sustainable Development Goals (SDGs), replacing the MDGs in ensuring global health security, well-being and economic prosperity for all.

Preventive chemotherapy as a strategy for elimination of neglected tropical parasitic diseases: endgame challenges.

PubMed

Bockarie, Moses J; Kelly-Hope, Louise A; Rebollo, Maria; Molyneux, David H

2013-08-05

Global efforts to address neglected tropical diseases (NTDs) were stimulated in January 2012 by the London declaration at which 22 partners, including the Bill & Melinda Gates Foundation, World Bank, World Health Organization (WHO) and major pharmaceutical companies committed to sustaining and expanding NTD programmes to eliminate or eradicate 11 NTDs by 2020 to achieve the goals outlined in the recently published WHO road map. Here, we present the current context of preventive chemotherapy for some NTDs, and discuss the problems faced by programmes as they consider the 'endgame', such as difficulties of access to populations in post-conflict settings, limited human and financial resources, and the need to expand access to clean water and improved sanitation for schistosomiasis and soil-transmitted helminthiasis. In the case of onchocerciasis and lymphatic filariasis, ivermectin treatment carries a significant risk owing to serious adverse effects in some patients co-infected with the tropical eye worm Loa loa filariasis. We discuss the challenges of managing complex partnerships, and maintain advocacy messages for the continued support for elimination of these preventable diseases.

Land use change and human health

NASA Astrophysics Data System (ADS)

Patz, Jonathan A.; Norris, Douglas E.

Disease emergence events have been documented following several types of land use change. This chapter reviews several health-relevant land use changes recognized today, including: 1) urbanization and urban sprawl; 2) water projects and agricultural development; 3) road construction and deforestation in the tropics; and 4) regeneration of temperate forests. Because habitat or climatic change substantially affects intermediate invertebrate hosts involved in many prevalent diseases, this chapter provides a basic description of vector-borne disease biology as a foundation for analyzing the effects of land use change. Urban sprawl poses health challenges stemming from heat waves exacerbated by the "urban heat island" effect, as well as from water contamination due to expanses of impervious road and concrete surfaces. Dams, irrigation and agricultural development have long been associated with diseases such as schistosomiasis and filariasis. Better management methods are required to address the trade-offs between expanded food production and altered habitats promoting deadly diseases. Deforestation can increase the nature and number of breeding sites for vector-borne diseases, such as malaria and onchocerciasis. Human host and disease vector interaction further increases risk, as can a change in arthropod-vector species composition.

Human infection patterns and heterogeneous exposure in river blindness

PubMed Central

Filipe, João A. N.; Boussinesq, Michel; Renz, Alfons; Collins, Richard C.; Vivas-Martinez, Sarai; Grillet, María-Eugenia; Little, Mark P.; Basáñez, María-Gloria

2005-01-01

Here we analyze patterns of human infection with Onchocerca volvulus (the cause of river blindness) in different continents and ecologies. In contrast with some geohelminths and schistosome parasites whose worm burdens typically exhibit a humped pattern with host age, patterns of O. volvulus infection vary markedly with locality. To test the hypothesis that such differences are partly due to heterogeneity in exposure to vector bites, we develop an age- and sex-structured model for intensity of infection, with parasite regulation within humans and vectors. The model is fitted to microfilarial data from savannah villages of northern Cameroon, coffee fincas of central Guatemala, and forest-dwelling communities of southern Venezuela that were recorded before introducing ivermectin treatment. Estimates of transmission and infection loads are compared with entomological and epidemiological field data. Host age- and sex-heterogeneous exposure largely explains locale-specific infection patterns in onchocerciasis (whereas acquired protective immunity has been invoked for other helminth infections). The basic reproductive number,R0, ranges from 5 to 8, which is slightly above estimates for other helminth parasites but well below previously presented values. PMID:16217028

Preventive chemotherapy as a strategy for elimination of neglected tropical parasitic diseases: endgame challenges

PubMed Central

Bockarie, Moses J.; Kelly-Hope, Louise A.; Rebollo, Maria; Molyneux, David H.

2013-01-01

Global efforts to address neglected tropical diseases (NTDs) were stimulated in January 2012 by the London declaration at which 22 partners, including the Bill & Melinda Gates Foundation, World Bank, World Health Organization (WHO) and major pharmaceutical companies committed to sustaining and expanding NTD programmes to eliminate or eradicate 11 NTDs by 2020 to achieve the goals outlined in the recently published WHO road map. Here, we present the current context of preventive chemotherapy for some NTDs, and discuss the problems faced by programmes as they consider the ‘endgame’, such as difficulties of access to populations in post-conflict settings, limited human and financial resources, and the need to expand access to clean water and improved sanitation for schistosomiasis and soil-transmitted helminthiasis. In the case of onchocerciasis and lymphatic filariasis, ivermectin treatment carries a significant risk owing to serious adverse effects in some patients co-infected with the tropical eye worm Loa loa filariasis. We discuss the challenges of managing complex partnerships, and maintain advocacy messages for the continued support for elimination of these preventable diseases. PMID:23798692

Interruption of Transmission of Onchocerca volvulus in the Oaxaca Focus, Mexico

PubMed Central

Rodríguez-Pérez, Mario A.; Unnasch, Thomas R.; Domínguez-Vázquez, Alfredo; Morales-Castro, Alba L.; Peña-Flores, Graciela P.; Orozco-Algarra, María E.; Arredondo-Jiménez, Juan I.; Richards, Frank; Vásquez-Rodríguez, Miguel A.; Rendón, Vidal García

2010-01-01

All endemic communities of the Oaxaca focus of onchocerciasis in southern Mexico have been treated annually or semi-annually with ivermectin since 1994. In-depth epidemiologic assessments were performed in communities during 2007 and 2008. None of the 52,632 Simulium ochraceum s.l. collected in four sentinel communities was found to contain parasite DNA when tested by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), resulting in an upper bound of the infection rate in the vectors of 0.07/2,000. The prevalence of microfilariae (mf) in the cornea and/or anterior chamber of the eye was also zero (0 of 1,039 residents examined; 95%-UL = 0.35%). Similarly, all 1,164 individuals examined by skin biopsy were mf negative (95%-UL = 0.31%), and sera collected from 3,569 children from 25 communities did not harbor Ov16 IgG4-antibodies (95%-UL = 0.09%). These meet the criteria for absence of morbidity and parasite transmission in the Oaxaca focus. As a result mass treatments with ivermectin were halted in 2009. PMID:20595472

Community-directed interventions for priority health problems in Africa: results of a multicountry study.

PubMed

2010-07-01

To determine the extent to which the community-directed approach used in onchocerciasis control in Africa could effectively and efficiently provide integrated delivery of other health interventions. A three-year experimental study was undertaken in 35 health districts from 2005 to 2007 in seven research sites in Cameroon, Nigeria and Uganda. Four trial districts and one comparison district were randomly selected in each site. All districts had established ivermectin treatment programmes, and in the trial districts four other established interventions - vitamin A supplementation, use of insecticide-treated nets, home management of malaria and short-course, directly-observed treatment for tuberculosis patients - were progressively incorporated into a community-directed intervention (CDI) process. At the end of each of the three study years, we performed quantitative evaluations of intervention coverage and provider costs, as well as qualitative assessments of the CDI process. With the CDI strategy, significantly higher coverage was achieved than with other delivery approaches for all interventions except for short-course, directly-observed treatment. The coverage of malaria interventions more than doubled. The district-level costs of delivering all five interventions were lower in the CDI districts, but no cost difference was found at the first-line health facility level. Process evaluation showed that: (i) participatory processes were important; (ii) recurrent problems with the supply of intervention materials were a major constraint to implementation; (iii) the communities and community implementers were deeply committed to the CDI process; (iv) community implementers were more motivated by intangible incentives than by external financial incentives. The CDI strategy, which builds upon the core principles of primary health care, is an effective and efficient model for integrated delivery of appropriate health interventions at the community level in Africa.

Community-directed interventions for priority health problems in Africa: results of a multicountry study

PubMed Central

2010-01-01

Abstract Objective To determine the extent to which the community-directed approach used in onchocerciasis control in Africa could effectively and efficiently provide integrated delivery of other health interventions. Methods A three-year experimental study was undertaken in 35 health districts from 2005 to 2007 in seven research sites in Cameroon, Nigeria and Uganda. Four trial districts and one comparison district were randomly selected in each site. All districts had established ivermectin treatment programmes, and in the trial districts four other established interventions – vitamin A supplementation, use of insecticide-treated nets, home management of malaria and short-course, directly-observed treatment for tuberculosis patients – were progressively incorporated into a community-directed intervention (CDI) process. At the end of each of the three study years, we performed quantitative evaluations of intervention coverage and provider costs, as well as qualitative assessments of the CDI process. Findings With the CDI strategy, significantly higher coverage was achieved than with other delivery approaches for all interventions except for short-course, directly-observed treatment. The coverage of malaria interventions more than doubled. The district-level costs of delivering all five interventions were lower in the CDI districts, but no cost difference was found at the first-line health facility level. Process evaluation showed that: (i) participatory processes were important; (ii) recurrent problems with the supply of intervention materials were a major constraint to implementation; (iii) the communities and community implementers were deeply committed to the CDI process; (iv) community implementers were more motivated by intangible incentives than by external financial incentives. Conclusion The CDI strategy, which builds upon the core principles of primary health care, is an effective and efficient model for integrated delivery of appropriate health interventions at the community level in Africa. PMID:20616970

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence, Distribution, and Disease Burden

PubMed Central

Hotez, Peter J.; Kamath, Aruna

2009-01-01

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA's malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA's poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world's number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region's agricultural productivity. There is a dearth of information on Africa's non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa's NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur. PMID:19707588

Repurposing and Reformulation of the Antiparasitic Agent Flubendazole for Treatment of Cryptococcal Meningoencephalitis, a Neglected Fungal Disease

PubMed Central

Nixon, Gemma L.; McEntee, Laura; Johnson, Adam; Farrington, Nicola; Whalley, Sarah; Livermore, Joanne; Natal, Cristien; Washbourn, Gina; Bibby, Jaclyn; Berry, Neil; Lestner, Jodi; Truong, Megan; Owen, Andrew; Lalloo, David; Charles, Ian

2018-01-01

ABSTRACT Current therapeutic options for cryptococcal meningitis are limited by toxicity, global supply, and emergence of resistance. There is an urgent need to develop additional antifungal agents that are fungicidal within the central nervous system and preferably orally bioavailable. The benzimidazoles have broad-spectrum antiparasitic activity but also have in vitro antifungal activity that includes Cryptococcus neoformans. Flubendazole (a benzimidazole) has been reformulated by Janssen Pharmaceutica as an amorphous solid drug nanodispersion to develop an orally bioavailable medicine for the treatment of neglected tropical diseases such as onchocerciasis. We investigated the in vitro activity, the structure-activity-relationships, and both in vitro and in vivo pharmacodynamics of flubendazole for cryptococcal meningitis. Flubendazole has potent in vitro activity against Cryptococcus neoformans, with a modal MIC of 0.125 mg/liter using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. Computer models provided an insight into the residues responsible for the binding of flubendazole to cryptococcal β-tubulin. Rapid fungicidal activity was evident in a hollow-fiber infection model of cryptococcal meningitis. The solid drug nanodispersion was orally bioavailable in mice with higher drug exposure in the cerebrum. The maximal dose of flubendazole (12 mg/kg of body weight/day) orally resulted in an ∼2 log10CFU/g reduction in fungal burden compared with that in vehicle-treated controls. Flubendazole was orally bioavailable in rabbits, but there were no quantifiable drug concentrations in the cerebrospinal fluid (CSF) or cerebrum and no antifungal activity was demonstrated in either CSF or cerebrum. These studies provide evidence for the further study and development of the benzimidazole scaffold for the treatment of cryptococcal meningitis. PMID:29311092

The lack of influence of food and local alcoholic brew on the blood level of Mectizan(®) (ivermectin).

PubMed

Homeida, Mamoun M; Malcolm, Stephen B; ElTayeb, A Z; Eversole, Rob R; Elassad, Asma S; Geary, Timothy G; Ali, Magdi M; Mackenzie, Charles D

2013-08-01

There is concern that extraneous factors, such as food and drink, may alter the pharmacodynamics of Mectizan(®) (ivermectin) in patients receiving this important anti-parasitic drug, and thus might put such individuals in danger of serious adverse events. The effects of a common local alcohol-containing beverage and a local food on plasma levels of ivermectin were studied in Sudanese volunteers after administration of the standard dose used in mass drug administration programs for onchocerciasis and filariasis. Plasma levels of ivermectin at various time points (0-48h) after administration of ivermectin were ascertained by HPLC assay in ten volunteers given 150μgkg(-1) ivermectin together with either a local sorghum-based food ('assida'), or a locally brewed alcoholic beverage ('arangi' made from sorghum grain) or in those who were fasting. Maximum mean (±SD) plasma levels of ivermectin (67±49ngml(-1)) were reached within 2h in fasting patients, and had dropped to 26±20ngml(-1) after 30h. The coadministration of local food or alcoholic beverage did not cause an increase in ivermectin plasma levels above those observed in people who were fasting. However, at 2h after ivermectin administration, patients given alcohol had significantly lower plasma ivermectin levels than fed patients or fasting patients. There were no significant differences among treatments for AUC0-30, Cmax, or tmax, and so the coadministration of local food or alcoholic beverage did not cause any change in pharmacokinetic parameters of ivermectin in the plasma in comparison with fasting. None of the measured levels of plasma ivermectin were greater than those reported in previous studies with this compound. These findings do not support the hypothesis that acute intake of alcohol is an important factor in the development of the serious adverse reactions that can occur during the treatment of loaisis patients with ivermectin (Mectizan(®)). Copyright © 2013 Elsevier B.V. All rights reserved.

Neglected tropical diseases and the millennium development goals: why the "other diseases" matter: reality versus rhetoric.

PubMed

Molyneux, David H; Malecela, Mwele N

2011-12-13

Since 2004 there has been an increased recognition of the importance of Neglected Tropical Diseases (NTDs) as impediments to development. These diseases are caused by a variety of infectious agents - viruses, bacteria and parasites - which cause a diversity of clinical conditions throughout the tropics. The World Health Organisation (WHO) has defined seventeen of these conditions as core NTDs. The objectives for the control, elimination or eradication of these conditions have been defined in World Health Assembly resolutions whilst the strategies for the control or elimination of individual diseases have been defined in various WHO documents. Since 2005 there has been a drive for the expanded control of these diseases through an integrated approach of mass drug administration referred to as Preventive Chemotherapy via community-based distribution systems and through schools. This has been made possible by donations from major pharmaceutical companies of quality and efficacious drugs which have a proven track record of safety. As a result of the increased commitment of endemic countries, bilateral donors and non-governmental development organisations, there has been a considerable expansion of mass drug administration. In particular, programmes targeting lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma and soil transmitted helminth infections have expanded to treat 887. 8 million people in 2009. There has been significant progress towards guinea worm eradication, and the control of leprosy and human African trypanosomiasis. This paper responds to what the authors believe are inappropriate criticisms of these programmes and counters accusations of the motives of partners made in recently published papers. We provide a detailed response and update the information on the numbers of global treatments undertaken for NTDs and list the success stories to date.The paper acknowledges that in undertaking any health programme in environments such as post-conflict countries, there are always challenges. It is also recognised that NTD control must always be undertaken within the health system context. However, it is important to emphasise that the availability of donated drugs, the multiple impact of those drugs, the willingness of countries to undertake their distribution, thereby committing their own resources to the programmes, and the proven beneficial results outweigh the problems which are faced in environments where communities are often beyond the reach of health services. Given the availability of these interventions, their cost effectiveness and the broader development impact we believe it would be unethical not to continue programmes of such long term benefit to the "bottom billion".

The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji.

PubMed

Kimura, Eisaku

2011-03-01

Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission.From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 µg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole included in the combination chemotherapy produced "beyond-filariasis" benefits: clearance/reduction of intestinal helminths, and, additionally, in the case of ivermectin, skin-dwelling ectoparasites.The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started its worldwide activities in 2000, with the target of elimination by 2020. The basic strategy is to conduct annual single-dose MDAs for 4-6 years. In 2000-2007, a minimum of 570 million individuals were treated in 48 of 83 endemic countries. The drugs used are DEC 6 mg/kg plus albendazole 400 mg in most countries, or ivermectin 200-400 µg/kg plus albendazole 400 mg particularly in onchocerciasis endemic countries in Africa. (MDAs with DEC alone had been used in India.)The GPELF achieved impressive results in terms of parasitological cure/improvement, clinical benefits, social and economic impacts, etc. However, the most impressive result of all was the programme's success in mobilizing hundreds of millions of local people, who not only took drugs but many of them actively supported MDAs as drug distributors and volunteers. Beyond filariasis, the role people can play in supplementing rural health services is now a topic of discussion and a source of hope for a new sustainable system.

Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda

PubMed Central

2011-01-01

Background Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of existing public health legislation. Conclusion While it has been an achievement to have offered free drugs to so many adults, current standard practices of monitoring, evaluation and delivery of MDA for NTDs are inconsistent and inadequate. Efforts to integrate programmes have exacerbated the difficulties. Improved assessment of what is really happening on the ground will be an essential step in achieving long-term overall reduction of the NTD burden for impoverished communities. PMID:21211001

Stability and change in the distribution of cytospecies of the Simulium damnosum complex (Diptera: Simuliidae) in southern Ghana from 1971 to 2011.

PubMed

Post, Rory J; Cheke, Robert A; Boakye, Daniel A; Wilson, Michael D; Osei-Atweneboana, Mike Y; Tetteh-Kumah, Anthony; Lamberton, Poppy Hl; Crainey, J Lee; Yaméogo, Laurent; Basáñez, María-Gloria

2013-07-13

Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species that have been described on the basis of differences in their larval polytene chromosomes. These (cyto) species differ in their geographical distributions, ecologies and epidemiological roles. In Ghana, distributional changes have been recorded as a consequence of vector control and environmental change (e.g. deforestation), with potential disease consequences. We review the distribution of cytospecies in southern Ghana and report changes observed with reference to historical data collated from 1971 to 2005 and new identifications made between 2006 and 2011. Larvae were collected from riverine breeding sites, fixed in Carnoy's solution and chromosome preparations made. Cytotaxonomic identifications from 1,232 samples (including 49 new samples) were analysed. We report long-term stability in cytospecies distribution in the rivers Afram, Akrum, Pawnpawn and Pru. For the rivers Oda, Ofin and Tano we describe (for the first time) patterns of distribution. We could not detect cytospecies composition changes in the upper Pra, and the lower Pra seems to have been stable. The elimination of the Djodji form of S. sanctipauli in the Volta Region seems to have had no long-term effects on the distribution of the other cytospecies, despite an initial surge by S. yahense. There has been a recent increase in the occurrence of savannah cytospecies in the river Asukawkaw, and this might be related to continuing deforestation. Cytospecies' distributions have not been stable from 1971 to 2011. Although there are no obvious causes for the temporary appearance and subsequent disappearance of cytospecies in a particular location, a major influence has been vector control and migration patterns, probably explaining observed changes on the Black Volta and lower Volta rivers. Deforestation was previously implicated in an increase of savannah cytospecies in southern Ghana (1975-1997). Our data had little power to support (or refute) suggestions of a continuing increase, except in the Asukawkaw river basin.

Stability and change in the distribution of cytospecies of the Simulium damnosum complex (Diptera: Simuliidae) in southern Ghana from 1971 to 2011

PubMed Central

2013-01-01

Background Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species that have been described on the basis of differences in their larval polytene chromosomes. These (cyto) species differ in their geographical distributions, ecologies and epidemiological roles. In Ghana, distributional changes have been recorded as a consequence of vector control and environmental change (e.g. deforestation), with potential disease consequences. We review the distribution of cytospecies in southern Ghana and report changes observed with reference to historical data collated from 1971 to 2005 and new identifications made between 2006 and 2011. Methods/Results Larvae were collected from riverine breeding sites, fixed in Carnoy’s solution and chromosome preparations made. Cytotaxonomic identifications from 1,232 samples (including 49 new samples) were analysed. We report long-term stability in cytospecies distribution in the rivers Afram, Akrum, Pawnpawn and Pru. For the rivers Oda, Ofin and Tano we describe (for the first time) patterns of distribution. We could not detect cytospecies composition changes in the upper Pra, and the lower Pra seems to have been stable. The elimination of the Djodji form of S. sanctipauli in the Volta Region seems to have had no long-term effects on the distribution of the other cytospecies, despite an initial surge by S. yahense. There has been a recent increase in the occurrence of savannah cytospecies in the river Asukawkaw, and this might be related to continuing deforestation. Conclusions Cytospecies’ distributions have not been stable from 1971 to 2011. Although there are no obvious causes for the temporary appearance and subsequent disappearance of cytospecies in a particular location, a major influence has been vector control and migration patterns, probably explaining observed changes on the Black Volta and lower Volta rivers. Deforestation was previously implicated in an increase of savannah cytospecies in southern Ghana (1975–1997). Our data had little power to support (or refute) suggestions of a continuing increase, except in the Asukawkaw river basin. PMID:23849451

Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis, and malaria: scientific links.

PubMed

Simon, G G

2016-01-01

The neglected tropical diseases (NTDs) are the most common infections of humans in Sub-Saharan Africa. Virtually all of the population living below the World Bank poverty figure is affected by one or more NTDs. New evidence indicates a high degree of geographic overlap between the highest-prevalence NTDs (soil-transmitted helminths, schistosomiasis, onchocerciasis, lymphatic filariasis, and trachoma) and malaria and HIV, exhibiting a high degree of co-infection. Recent research suggests that NTDs can affect HIV and AIDS, tuberculosis (TB), and malaria disease progression. A combination of immunological, epidemiological, and clinical factors can contribute to these interactions and add to a worsening prognosis for people affected by HIV/AIDS, TB, and malaria. Together these results point to the impacts of the highest-prevalence NTDs on the health outcomes of malaria, HIV/AIDS, and TB and present new opportunities to design innovative public health interventions and strategies for these 'big three' diseases. This analysis describes the current findings of research and what research is still needed to strengthen the knowledge base of the impacts NTDs have on the big three. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Zoonotic helminths affecting the human eye

PubMed Central

2011-01-01

Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths that affect human eyes (HIE) may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis), food consumption (sparganosis, trichinellosis) and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis). Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs) or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt Seneca Ep 6,5 Men believe their eyes more than their ears PMID:21429191

The MSFC Program Control Development Program

NASA Technical Reports Server (NTRS)

1994-01-01

It is the policy of the Marshall Space Flight Center (MSFC) that employees be given the opportunity to develop their individual skills and realize their full potential consistent with their selected career path and with the overall Center's needs and objectives. The MSFC Program Control Development Program has been designed to assist individuals who have selected Program Control or Program Analyst Program Control as a career path to achieve their ultimate career goals. Individuals selected to participate in the MSFC Program Control Development Program will be provided with development training in the various Program Control functional areas identified in the NASA Program Control Model. The purpose of the MSFC Program Control Development Program is to develop individual skills in the various Program Control functions by on-the-job and classroom instructional training on the various systems, tools, techniques, and processes utilized in these areas.

Innovation for the 'bottom 100 million': eliminating neglected tropical diseases in the Americas.

PubMed

Hotez, Peter J; Dumonteil, Eric; Heffernan, Michael J; Bottazzi, Maria E

2013-01-01

An estimated 100 million people in the Latin American and Caribbean (LAC) region live on less than US$2 per day, while another 46 million people in the US live below that nation's poverty line. Almost all of the 'bottom 100 million' people suffer from at least one neglected tropical disease (NTD), including one-half of the poorest people in the region infected with hookworms, 10% with Chagas disease, and up to 1-2% with dengue, schistosomiasis, and/or leishmaniasis. In the US, NTDs such as Chagas disease, cysticercosis, toxocariasis, and trichomoniasis are also common among poor populations. These NTDs trap the poorest people in the region in poverty, because of their impact on maternal and child health, and occupational productivity. Through mass drug administration (MDA), several NTDs are on the verge of elimination in the Americas, including lymphatic filariasis, onchocerciasis, trachoma, and possibly leprosy. In addition, schistosomiasis may soon be eliminated in the Caribbean. However, for other NTDs including hookworm infection, Chagas disease, dengue, schistosomiasis, and leishmaniasis, a new generation of 'anti-poverty vaccines' will be required. Several vaccines for dengue are under development by multinational pharmaceutical companies, whereas others are being pursued through non-profit product development partnerships (PDPs), in collaboration with developing country manufacturers in Brazil and Mexico. The Sabin Vaccine Institute PDP is developing a primarily preventive bivalent recombinant human hookworm vaccine, which is about to enter phase 1 clinical testing in Brazil, as well as a new therapeutic Chagas disease vaccine in collaboration with several Mexican institutions. The Chagas disease vaccine would be administered to seropositive patients to delay or prevent the onset of Chagasic cardiomyopathy (secondary prevention). Together, MDA and the development of new anti-poverty vaccines afford an opportunity to implement effective control and elimination strategies for the major NTDs in the Americas.

Oligonucleotide Based Magnetic Bead Capture of Onchocerca volvulus DNA for PCR Pool Screening of Vector Black Flies

PubMed Central

Gopal, Hemavathi; Hassan, Hassan K.; Rodríguez-Pérez, Mario A.; Toé, Laurent D.; Lustigman, Sara; Unnasch, Thomas R.

2012-01-01

Background Entomological surveys of Simulium vectors are an important component in the criteria used to determine if Onchocerca volvulus transmission has been interrupted and if focal elimination of the parasite has been achieved. However, because infection in the vector population is quite rare in areas where control has succeeded, large numbers of flies need to be examined to certify transmission interruption. Currently, this is accomplished through PCR pool screening of large numbers of flies. The efficiency of this process is limited by the size of the pools that may be screened, which is in turn determined by the constraints imposed by the biochemistry of the assay. The current method of DNA purification from pools of vector black flies relies upon silica adsorption. This method can be applied to screen pools containing a maximum of 50 individuals (from the Latin American vectors) or 100 individuals (from the African vectors). Methodology/Principal Findings We have evaluated an alternative method of DNA purification for pool screening of black flies which relies upon oligonucleotide capture of Onchocerca volvulus genomic DNA from homogenates prepared from pools of Latin American and African vectors. The oligonucleotide capture assay was shown to reliably detect one O. volvulus infective larva in pools containing 200 African or Latin American flies, representing a two-four fold improvement over the conventional assay. The capture assay requires an equivalent amount of technical time to conduct as the conventional assay, resulting in a two-four fold reduction in labor costs per insect assayed and reduces reagent costs to $3.81 per pool of 200 flies, or less than $0.02 per insect assayed. Conclusions/Significance The oligonucleotide capture assay represents a substantial improvement in the procedure used to detect parasite prevalence in the vector population, a major metric employed in the process of certifying the elimination of onchocerciasis. PMID:22724041

Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya.

PubMed

Njenga, S M; Wamae, C N; Njomo, D W; Mwandawiro, C S; Molyneux, D H

2008-10-01

Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.

Global Change and Human Vulnerability to Vector-Borne Diseases

PubMed Central

Sutherst, Robert W.

2004-01-01

Global change includes climate change and climate variability, land use, water storage and irrigation, human population growth and urbanization, trade and travel, and chemical pollution. Impacts on vector-borne diseases, including malaria, dengue fever, infections by other arboviruses, schistosomiasis, trypanosomiasis, onchocerciasis, and leishmaniasis are reviewed. While climate change is global in nature and poses unknown future risks to humans and natural ecosystems, other local changes are occurring more rapidly on a global scale and are having significant effects on vector-borne diseases. History is invaluable as a pointer to future risks, but direct extrapolation is no longer possible because the climate is changing. Researchers are therefore embracing computer simulation models and global change scenarios to explore the risks. Credible ranking of the extent to which different vector-borne diseases will be affected awaits a rigorous analysis. Adaptation to the changes is threatened by the ongoing loss of drugs and pesticides due to the selection of resistant strains of pathogens and vectors. The vulnerability of communities to the changes in impacts depends on their adaptive capacity, which requires both appropriate technology and responsive public health systems. The availability of resources in turn depends on social stability, economic wealth, and priority allocation of resources to public health. PMID:14726459

Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda.

PubMed

Lagoro, David Kitara; Arony, Denis Anywar

2017-01-01

Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus ( OV ). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus . Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis , some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with ( OV infection (using positive skin snips), we observe that ( OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda.

Nodding syndrome (NS) and Onchocerca Volvulus (OV) in Northern Uganda

PubMed Central

Lagoro, David Kitara; Arony, Denis Anywar

2017-01-01

Nodding Syndrome (NS) is a childhood neurological disorder characterized by atonic seizures, cognitive decline, school dropout, muscle weakness, thermal dysfunction, wasting and stunted growth. There are recent published information suggesting associations between Nodding Syndrome (NS) with cerebrospinal fluid (CSF) VGKC antibodies and serum leiomidin-1 antibody cross reacting with Onchocerca Volvulus (OV). These findings suggest a neuro-inflammatory cause of NS and they are important findings in the search for the cause of Nodding Syndrome. These observations perhaps provide further, the unique explanation for the association between Nodding Syndrome and Onchocerca Volvulus. Many clinical and epidemiological studies had shown a significant correlation between NS and infestation with a nematode, Onchocerca volvulus which causes a disease, Onchocerciasis, some of which when left untreated can develop visual defect ("River Blindness"). While these studies conducted in Northern Uganda and Southern Sudan indicate a statistically significant association with (OV infection (using positive skin snips), we observe that (OV is generally endemic in many parts of Sub Saharan Africa and Latin America and that to date, no NS cases have been recorded in those regions. This letter to the Editor is to provide additional information on the current view about the relationship between Nodding Syndrome and Onchocerca Volvulus as seen in Northern Uganda. PMID:29138647

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers.

PubMed

Muñoz, Jose; Ballester, Maria Rosa; Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia; Krolewiecki, Alejandro J

2018-01-01

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. ClinicalTrials.gov NCT03173742.

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers

PubMed Central

Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia

2018-01-01

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study. These findings contribute to further understand the pharmacokinetic characteristics of ivermectin, highlighting its safety across different dosing regimens. They also correlate with known pharmacokinetic parameters showing stable levels of AUC and Cmax across a wide range of body weights, which justifies the strategy of fix dosing from a pharmacokinetic perspective. Trial registration ClinicalTrials.gov NCT03173742. PMID:29346388

Quadratic Programming for Allocating Control Effort

NASA Technical Reports Server (NTRS)

Singh, Gurkirpal

2005-01-01

A computer program calculates an optimal allocation of control effort in a system that includes redundant control actuators. The program implements an iterative (but otherwise single-stage) algorithm of the quadratic-programming type. In general, in the quadratic-programming problem, one seeks the values of a set of variables that minimize a quadratic cost function, subject to a set of linear equality and inequality constraints. In this program, the cost function combines control effort (typically quantified in terms of energy or fuel consumed) and control residuals (differences between commanded and sensed values of variables to be controlled). In comparison with prior control-allocation software, this program offers approximately equal accuracy but much greater computational efficiency. In addition, this program offers flexibility, robustness to actuation failures, and a capability for selective enforcement of control requirements. The computational efficiency of this program makes it suitable for such complex, real-time applications as controlling redundant aircraft actuators or redundant spacecraft thrusters. The program is written in the C language for execution in a UNIX operating system.

Program control for mission success

NASA Technical Reports Server (NTRS)

Longanecker, G. W.

1994-01-01

This article suggests that in order to be able to exercise control over a particular program, the program itself must be controllable. A controllable program therefore, according to the author, is one that has been properly scoped technically, realistically scheduled, and adequately budgeted. The article delves indepth into each of the above aspects of a controllable program and discusses both the pros and cons of each.

Vector control activities: Fiscal Year, 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-04-01

The program is divided into two major components - operations and support studies. The support studies are designed to improve the operational effectiveness and efficiency of the control program and to identify other vector control problems requiring TVA attention and study. Nonchemical methods of control are emphasized and are supplemented with chemical measures as needed. TVA also cooperates with various concerned municipalities in identifying blood-sucking arthropod pest problems and demonstrating control techniques useful in establishing abatement programs, and provides technical assistance to other TVA programs and organizations. The program also helps Land Between The Lakes (LBL) plan and conduct vectormore » control operations and tick control research. Specific program control activities and support studies are discussed.« less

48 CFR 519.7014 - Internal controls.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Internal controls. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7014 Internal controls. (a) The GSA Mentor-Protégé Program Manager will manage the Program. Internal controls will be established by...

48 CFR 519.7014 - Internal controls.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Internal controls. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7014 Internal controls. (a) The GSA Mentor-Protégé Program Manager will manage the Program. Internal controls will be established by...

48 CFR 519.7014 - Internal controls.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Internal controls. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7014 Internal controls. (a) The GSA Mentor-Protégé Program Manager will manage the Program. Internal controls will be established by...

48 CFR 519.7014 - Internal controls.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Internal controls. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7014 Internal controls. (a) The GSA Mentor-Protégé Program Manager will manage the Program. Internal controls will be established by...

48 CFR 519.7014 - Internal controls.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Internal controls. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7014 Internal controls. (a) The GSA Mentor-Protégé Program Manager will manage the Program. Internal controls will be established by...

Propulsion control experience used in the Highly Integrated Digital Electronic Control (HIDEC) program

NASA Technical Reports Server (NTRS)

Myers, L. P.; Burcham, F. W., Jr.

1984-01-01

The highly integrated digital electronic control (HIDEC) program will integrate the propulsion and flight control systems on an F-15 airplane at NASA Ames Research Center's Dryden Flight Research Facility. Ames-Dryden has conducted several propulsion control programs that have contributed to the HIDEC program. The digital electronic engine control (DEEC) flight evaluation investigated the performance and operability of the F100 engine equipped with a full-authority digital electronic control system. Investigations of nozzle instability, fault detection and accommodation, and augmentor transient capability provided important information for the HIDEC program. The F100 engine model derivative (EMD) was also flown in the F-15 airplane, and airplane performance was significantly improved. A throttle response problem was found and solved with a software fix to the control logic. For the HIDEC program, the F100 EMD engines equipped with DEEC controls will be integrated with the digital flight control system. The control modes to be implemented are an integrated flightpath management mode and an integrated adaptive engine control system mode. The engine control experience that will be used in the HIDEC program is discussed.

Generic command interpreter for robot controllers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werner, J.

1991-04-09

Generic command interpreter programs have been written for robot controllers at Sandia National Laboratories (SNL). Each interpreter program resides on a robot controller and interfaces the controller with a supervisory program on another (host) computer. We call these interpreter programs monitors because they wait, monitoring a communication line, for commands from the supervisory program. These monitors are designed to interface with the object-oriented software structure of the supervisory programs. The functions of the monitor programs are written in each robot controller's native language but reflect the object-oriented functions of the supervisory programs. These functions and other specifics of the monitormore » programs written for three different robots at SNL will be discussed. 4 refs., 4 figs.« less

Species differences in hepatic biotransformation of the anthelmintic drug flubendazole.

PubMed

Maté, M L; Geary, T; Mackenzie, C; Lanusse, C; Virkel, G

2017-10-01

Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl-reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red-FLBZ). The rate of microsomal red-FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red-FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red-FLBZ to FLBZ in a NADP + -dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red-FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species. © 2017 John Wiley & Sons Ltd.

Social stigma towards neglected tropical diseases: a systematic review.

PubMed

Hofstraat, Karlijn; van Brakel, Wim H

2016-03-01

People affected by neglected tropical diseases (NTDs) are frequently the target of social stigmatization. To date not much attention has been given to stigma in relation to NTDs. The objective of this review is to identify the extent of social stigma and the similarities and differences in the causes, manifestations, impact of stigma and interventions used between the NTDs. A systematic review was conducted in Pubmed, ScienceDirect, PsycINFO and Web of Knowledge. The search encompassed 17 NTDs, including podoconiosis, but not leprosy as this NTD has recently been reviewed. However, leprosy was included in the discussion. The 52 selected articles provided evidence on stigma related to lymphatic filariasis (LF), podoconiosis, Buruli ulcer, onchocerciasis, schistosomiasis, leishmaniasis, Chagas disease, trachoma, soil-transmitted helminthiasis (STH) and human African trypanosomiasis. The similarities predominated in stigma related to the various NTDs; only minimal differences in stigma reasons and measures were found. These similarities suggest that joint approaches to reduce stigmatization may be feasible. Lessons from leprosy and other stigmatized health conditions can be used to plan such joint approaches. Further research will be necessary to study the efficacy of joint interventions and to investigate stigma related to NTDs for which no evidence is available yet. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Human Parasitology and Parasitic Diseases: Heading Towards 2050.

PubMed

Hotez, Peter J

2018-01-01

By 2050 our civilized planet may be comprised predominantly of networked megacities embedded in warm subtropical and tropical climates, and under stress from climate change and catastrophic weather events. Urban slum areas in these cities, including those found in wealthier middle- and high-income nations (blue marble health), will be especially vulnerable to disease. Moreover, regional conflicts fought over shifting and limited resources, including water, will collapse health systems infrastructures to further promote disease emergence and reemergence. Thus while by 2050 we might congratulate ourselves for successfully eliminating some key parasitic and neglected tropical diseases such as dracunculiasis, lymphatic filariasis, onchocerciasis, and human African trypanosomiasis, there could be a commensurate rise in other parasitic diseases based on the scenarios highlighted above. Of particular concern are urban and newly urbanized helminth infections, including schistosomiasis and some soil-transmitted helminth infections, as well zoonotic helminthiases, such as toxocariasis, food-borne trematodiases, and cysticercosis. Protozoan infections persisting in urban environments, including leishmaniasis, Chagas disease, malaria, and intestinal protozoan infections, will also remain, as will zoonotic diseases such as toxoplasmosis. Our best hope to counteract the parasitic diseases emerging in our steaming 21st century megacities is to develop new and innovative technologies through gene editing, systems biology, and immunology, and the new single-celled OMICs. However, success on this front will require our ability to contain the globalization of antiscience beliefs and sentiments. © 2018 Elsevier Ltd All rights reserved.

Assessing the present state and potential of Medicaid controlled substance lock-in programs.

PubMed

Roberts, Andrew W; Skinner, Asheley Cockrell

2014-05-01

Nonmedical use of prescription medications--particularly controlled substances--has risen dramatically in recent decades, resulting in alarming increases in overdose-related health care utilization, costs, and mortality. The Centers for Disease Control and Prevention estimate that 80% of abused and misused controlled substances originate as legal prescriptions. As such, policymakers and payers have the opportunity to combat nonmedical use by regulating controlled substance accessibility within legal prescribing and dispensing processes. One common policy strategy is found in Medicaid controlled substance lock-in programs. Lock-in programs identify Medicaid beneficiaries exhibiting high-risk controlled substance seeking behavior and "lock in" these patients to, typically, a single prescriber and pharmacy from which they may obtain Medicaid-covered controlled substance prescriptions. Lock-in restrictions are intended to improve care coordination between providers, reduce nonmedical use behaviors, and limit Medicaid costs stemming from nonmedical use and diversion. Peer-reviewed and gray literature have been examined to assess the current prevalence and design of Medicaid lock-in programs, as well as the current evidence base for informing appropriate program design and understanding program effectiveness. Forty-six state Medicaid agencies currently operate lock-in programs. Program design varies widely between states in terms of defining high-risk controlled substance use, the scope of actual lock-in restrictions, and length of program enrollment. Additionally, there is a remarkable dearth of peer-reviewed literature evaluating the design and effectiveness of Medicaid lock-in programs. Nearly all outcomes evidence stemmed from publicly accessible internal Medicaid program evaluations, which largely investigated cost savings to the state. Lock-in programs are highly prevalent and poised to play a meaningful role in curbing the prescription drug abuse epidemic. However, achieving these ends requires a concerted effort from the academic and policy communities to rigorously evaluate the effect of lock-in programs on patient outcomes, determine optimal program design, and explore opportunities to enhance lock-in program impact through coordination with parallel controlled substance policy efforts, namely prescription drug-monitoring programs.

7 CFR 58.147 - Insect and rodent control program.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

48 CFR 819.7112 - Internal controls.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Internal controls. 819... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7112 Internal controls. (a) OSDBU... Program objectives. OSDBU will establish internal controls as checks and balances applicable to the...

48 CFR 819.7112 - Internal controls.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Internal controls. 819... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7112 Internal controls. (a) OSDBU... Program objectives. OSDBU will establish internal controls as checks and balances applicable to the...

48 CFR 819.7112 - Internal controls.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Internal controls. 819... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7112 Internal controls. (a) OSDBU... Program objectives. OSDBU will establish internal controls as checks and balances applicable to the...

48 CFR 819.7112 - Internal controls.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Internal controls. 819... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7112 Internal controls. (a) OSDBU... Program objectives. OSDBU will establish internal controls as checks and balances applicable to the...

7 CFR 58.147 - Insect and rodent control program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

Users manual for flight control design programs

NASA Technical Reports Server (NTRS)

Nalbandian, J. Y.

1975-01-01

Computer programs for the design of analog and digital flight control systems are documented. The program DIGADAPT uses linear-quadratic-gaussian synthesis algorithms in the design of command response controllers and state estimators, and it applies covariance propagation analysis to the selection of sampling intervals for digital systems. Program SCHED executes correlation and regression analyses for the development of gain and trim schedules to be used in open-loop explicit-adaptive control laws. A linear-time-varying simulation of aircraft motions is provided by the program TVHIS, which includes guidance and control logic, as well as models for control actuator dynamics. The programs are coded in FORTRAN and are compiled and executed on both IBM and CDC computers.

Development of a Biological Control Program for Eurasian Watermilfoil (Myriophyllum spicatum)

DTIC Science & Technology

2008-08-01

spicatum). Rawalpindi: Pakistan Station Commonwealth Institute of Biological Control. Gleason, H. A ., and A . Cronquist . 1991. Manual of vascular plants...ER D C/ EL T R- 08 -2 2 Aquatic Plant Control Research Program Development of a Biological Control Program for Eurasian Watermilfoil... a Biological Control Program for Eurasian Watermilfoil (Myriophyllum spicatum) Matthew J. W. Cock, Hariet L. Hinz, Gitta Grosskopf, and Patrick

7 CFR 58.149 - Alternate quality control programs for dairy products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Alternate quality control programs for dairy products... and Grading Service 1 Operations and Operating Procedures § 58.149 Alternate quality control programs for dairy products. (a) When a plant has in operation an acceptable quality control program which is...

7 CFR 58.247 - Insect and rodent control program.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program as...

Knowledge Gaps Impacting the Development of Bovine Viral Diarrhea Virus Control Programs in the United States

USDA-ARS?s Scientific Manuscript database

This paper identifies knowledge gaps that impact on the design of programs to control and or eradicate bovine viral diarrhea viruses (BVDV) in the United States. Currently there are several voluntary regional BVDV control programs in place. These control programs are aimed at the removal of animals ...

7 CFR 58.247 - Insect and rodent control program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program as...

Structural overview and learner control in hypermedia instructional programs

NASA Astrophysics Data System (ADS)

Burke, Patricia Anne

1998-09-01

This study examined the effects of a structural overview and learner control in a computer-based program on the achievement, attitudes, time in program and Linearity of path of fifth-grade students. Four versions of a computer-based instructional program about the Sun and planets were created in a 2 x 2 factorial design. The program consisted of ten sections, one for each planet and one for the Sun. Two structural overview conditions (structural overview, no structural overview) were crossed with two control conditions (learner control, program control). Subjects in the structural overview condition chose the order in which they would learn about the planets from among three options: ordered by distance from the Sun, ordered by size, or ordered by temperature. Subjects in the learner control condition were able to move freely among screens within a section and to choose their next section after finishing the previous one. In contrast, those in the program control condition advanced through the program in a prescribed linear manner. A 2 x 2 ANOVA yielded no significant differences in posttest scores for either independent variable or for their interaction. The structural overview was most likely not effective because subjects spent only a small percentage of their total time on the structural overview screens and they were not required to act upon the information in those screens. Learner control over content sequencing may not have been effective because most learner-control subjects chose the same overall sequence of instruction (i.e., distance from the Sun) prescribed for program-control subjects. Learner-control subjects chose to view an average of 40 more screens than the fixed number of 160 screens in the program-control version. However, program-control subjects spent significantly more time per screen than learner-control subjects, and the total time in program did not differ significantly between the two groups. Learner-control subjects receiving the structural overview deviated from the linear path significantly more often than subjects who did not have the structural overview, but deviation from the linear path was not associated with higher posttest scores.

The KALI multi-arm robot programming and control environment

NASA Technical Reports Server (NTRS)

Backes, Paul; Hayati, Samad; Hayward, Vincent; Tso, Kam

1989-01-01

The KALI distributed robot programming and control environment is described within the context of its use in the Jet Propulsion Laboratory (JPL) telerobot project. The purpose of KALI is to provide a flexible robot programming and control environment for coordinated multi-arm robots. Flexibility, both in hardware configuration and software, is desired so that it can be easily modified to test various concepts in robot programming and control, e.g., multi-arm control, force control, sensor integration, teleoperation, and shared control. In the programming environment, user programs written in the C programming language describe trajectories for multiple coordinated manipulators with the aid of KALI function libraries. A system of multiple coordinated manipulators is considered within the programming environment as one motion system. The user plans the trajectory of one controlled Cartesian frame associated with a motion system and describes the positions of the manipulators with respect to that frame. Smooth Cartesian trajectories are achieved through a blending of successive path segments. The manipulator and load dynamics are considered during trajectory generation so that given interface force limits are not exceeded.

Benchmarking the Cost per Person of Mass Treatment for Selected Neglected Tropical Diseases: An Approach Based on Literature Review and Meta-regression with Web-Based Software Application

PubMed Central

Fitzpatrick, Christopher; Fleming, Fiona M.; Madin-Warburton, Matthew; Schneider, Timm; Meheus, Filip; Asiedu, Kingsley; Solomon, Anthony W.; Montresor, Antonio; Biswas, Gautam

2016-01-01

Background Advocacy around mass treatment for the elimination of selected Neglected Tropical Diseases (NTDs) has typically put the cost per person treated at less than US$ 0.50. Whilst useful for advocacy, the focus on a single number misrepresents the complexity of delivering “free” donated medicines to about a billion people across the world. We perform a literature review and meta-regression of the cost per person per round of mass treatment against NTDs. We develop a web-based software application (https://healthy.shinyapps.io/benchmark/) to calculate setting-specific unit costs against which programme budgets and expenditures or results-based pay-outs can be benchmarked. Methods We reviewed costing studies of mass treatment for the control, elimination or eradication of lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, onchocerciasis, trachoma and yaws. These are the main 6 NTDs for which mass treatment is recommended. We extracted financial and economic unit costs, adjusted to a standard definition and base year. We regressed unit costs on the number of people treated and other explanatory variables. Regression results were used to “predict” country-specific unit cost benchmarks. Results We reviewed 56 costing studies and included in the meta-regression 34 studies from 23 countries and 91 sites. Unit costs were found to be very sensitive to economies of scale, and the decision of whether or not to use local volunteers. Financial unit costs are expected to be less than 2015 US$ 0.50 in most countries for programmes that treat 100 thousand people or more. However, for smaller programmes, including those in the “last mile”, or those that cannot rely on local volunteers, both economic and financial unit costs are expected to be higher. Discussion The available evidence confirms that mass treatment offers a low cost public health intervention on the path towards universal health coverage. However, more costing studies focussed on elimination are needed. Unit cost benchmarks can help in monitoring value for money in programme plans, budgets and accounts, or in setting a reasonable pay-out for results-based financing mechanisms. PMID:27918573

A computational analysis of the binding mode of closantel as inhibitor of the Onchocerca volvulus chitinase: insights on macrofilaricidal drug design

NASA Astrophysics Data System (ADS)

Segura-Cabrera, Aldo; Bocanegra-García, Virgilio; Lizarazo-Ortega, Cristian; Guo, Xianwu; Correa-Basurto, José; Rodríguez-Pérez, Mario A.

2011-12-01

Onchocerciasis is a leading cause of blindness with at least 37 million people infected and more than 120 million people at risk of contracting the disease; most (99%) of this population, threatened by infection, live in Africa. The drug of choice for mass treatment is the microfilaricidal Mectizan® (ivermectin); it does not kill the adult stages of the parasite at the standard dose which is a single annual dose aimed at disease control. However, multiple treatments a year with ivermectin have effects on adult worms. The discovery of new therapeutic targets and drugs directed towards the killing of the adult parasites are thus urgently needed. The chitinase of filarial nematodes is a new drug target due to its essential function in the metabolism and molting of the parasite. Closantel is a potent and specific inhibitor of chitinase of Onchocerca volvulus (OvCHT1) and other filarial chitinases. However, the binding mode and specificity of closantel towards OvCHT1 remain unknown. In the absence of a crystallographic structure of OvCHT1, we developed a homology model of OvCHT1 using the currently available X-ray structures of human chitinases as templates. Energy minimization and molecular dynamics (MD) simulation of the model led to a high quality of 3D structure of OvCHIT1. A flexible docking study using closantel as the ligand on the binding site of OvCHIT1 and human chitinases was performed and demonstrated the differences in the closantel binding mode between OvCHIT1 and human chitinase. Furthermore, molecular dynamics simulations and free-energy calculation were employed to determine and compare the detailed binding mode of closantel with OvCHT1 and the structure of human chitinase. This comparative study allowed identification of structural features and properties responsible for differences in the computationally predicted closantel binding modes. The homology model and the closantel binding mode reported herein might help guide the rational development of novel drugs against the adult parasite of O. volvulus and such findings could be extrapolated to other filarial neglected diseases.

Benchmarking the Cost per Person of Mass Treatment for Selected Neglected Tropical Diseases: An Approach Based on Literature Review and Meta-regression with Web-Based Software Application.

PubMed

Fitzpatrick, Christopher; Fleming, Fiona M; Madin-Warburton, Matthew; Schneider, Timm; Meheus, Filip; Asiedu, Kingsley; Solomon, Anthony W; Montresor, Antonio; Biswas, Gautam

2016-12-01

Advocacy around mass treatment for the elimination of selected Neglected Tropical Diseases (NTDs) has typically put the cost per person treated at less than US$ 0.50. Whilst useful for advocacy, the focus on a single number misrepresents the complexity of delivering "free" donated medicines to about a billion people across the world. We perform a literature review and meta-regression of the cost per person per round of mass treatment against NTDs. We develop a web-based software application (https://healthy.shinyapps.io/benchmark/) to calculate setting-specific unit costs against which programme budgets and expenditures or results-based pay-outs can be benchmarked. We reviewed costing studies of mass treatment for the control, elimination or eradication of lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, onchocerciasis, trachoma and yaws. These are the main 6 NTDs for which mass treatment is recommended. We extracted financial and economic unit costs, adjusted to a standard definition and base year. We regressed unit costs on the number of people treated and other explanatory variables. Regression results were used to "predict" country-specific unit cost benchmarks. We reviewed 56 costing studies and included in the meta-regression 34 studies from 23 countries and 91 sites. Unit costs were found to be very sensitive to economies of scale, and the decision of whether or not to use local volunteers. Financial unit costs are expected to be less than 2015 US$ 0.50 in most countries for programmes that treat 100 thousand people or more. However, for smaller programmes, including those in the "last mile", or those that cannot rely on local volunteers, both economic and financial unit costs are expected to be higher. The available evidence confirms that mass treatment offers a low cost public health intervention on the path towards universal health coverage. However, more costing studies focussed on elimination are needed. Unit cost benchmarks can help in monitoring value for money in programme plans, budgets and accounts, or in setting a reasonable pay-out for results-based financing mechanisms.

Patent landscape of neglected tropical diseases: an analysis of worldwide patent families.

PubMed

Akinsolu, Folahanmi Tomiwa; de Paiva, Vitor Nobre; Souza, Samuel Santos; Varga, Orsolya

2017-11-14

"Neglected Tropical Diseases" (NTDs) affect millions of people in Africa, Asia and South America. The two primary ways of strategic interventions are "preventive chemotherapy and transmission control" (PCT), and "innovative and intensified disease management" (IDM). In the last 5 years, phenomenal progress has been achieved. However, it is crucial to intensify research effort into NTDs, because of the emerging drug resistance. According to the World Health Organization (WHO), the term NTDs covers 17 diseases, namely buruli ulcer, Chagas disease, dengue, dracunculiasis, echinococcosis, trematodiasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthes, taeniasis, trachoma, and yaws. The aim of this study is to map out research and development (R&D) landscape through patent analysis of these identified NTDs. To achieve this, analysis and evaluation have been conducted on patenting trends, current legal status of patent families, priority countries by earliest priority years and their assignee types, technological fields of patent families over time, and original and current patent assignees. Patent families were extracted from Patseer, an international database of patents from over 100 patent issuing authorities worldwide. Evaluation of the patents was carried out using the combination of different search terms related to each identified NTD. In this paper, a total number of 12,350 patent families were analyzed. The main countries with sources of inventions were identified to be the United States (US) and China. The main technological fields covered by NTDs patent landscape are pharmaceuticals, biotechnology, organic fine chemistry, analysis of biological materials, basic materials chemistry, and medical technology. Governmental institutions and universities are the primary original assignees. Among the NTDs, leishmaniasis, dengue, and rabies received the highest number of patent families, while human African trypanosomiasis (sleeping sickness), taeniasis, and dracunciliasis received the least. The overall trend of patent families shows an increase between 1985 and 2008, and followed by at least 6 years of stagnation. The filing pattern of patent families analyzed undoubtedly reveals slow progress on research and development of NTDs. Involving new players, such as non-governmental organizations may help to mitigate and reduce the burden of NTDs.

Dutch elm disease control: performance and costs

Treesearch

William N., Jr. Cannon; David P. Worley

1976-01-01

Municipal programs to suppress Dutch elm disease have had highly variable results. Performance as measured by tree mortality was unrelated to control strategies. Costs for control programs were 37 to 76 percent less than costs without control programs in the 15-year time-span of the study. Only those municipalities that conducted a high-performance program could be...

Dutch elm disease control: performance and costs

Treesearch

William N., Jr. Cannon; David P. Worley

1980-01-01

Municipal programs to suppress Dutch elm disease have had highly variable results. Performance as measured by tree mortality was unrelated to control strategies. Costs for control programs were 37 to 76 percent less than costs without control programs in the 15-year time-span of the study. Only those municipalities that conducted a high-performance program could be...

Steady-state simulation program for attitude control propulsion systems

NASA Technical Reports Server (NTRS)

Heinmiller, P. J.

1973-01-01

The formulation and the engineering equations employed in the steady state attitude control propulsion system simulation program are presented. The objective of this program is to aid in the preliminary design and development of propulsion systems used for spacecraft attitude control. The program simulates the integrated operation of the many interdependent components typically comprising an attitude control propulsion system. Flexibility, generality, ease of operation, and speed consistent with adequate accuracy were overriding considerations during the development of this program. Simulation modules were developed representing the various types of fluid components typically encountered in an attitude control propulsion system. These modules are basically self-contained and may be arranged by the program user into desired configuration through the program input data.

X-43A Flight Controls

NASA Technical Reports Server (NTRS)

Baumann, Ethan

2006-01-01

A viewgraph presentation detailing X-43A Flight controls at NASA Dryden Flight Research Center is shown. The topics include: 1) NASA Dryden, Overview and current and recent flight test programs; 2) Unmanned Aerial Vehicle Synthetic Aperture Radar (UAVSAR) Program, Program Overview and Platform Precision Autopilot; and 3) Hyper-X Program, Program Overview, X-43A Flight Controls and Flight Results.

An Introduction to Numerical Control. Problems for Numerical Control Part Programming.

ERIC Educational Resources Information Center

Campbell, Clifton P.

This combination text and workbook is intended to introduce industrial arts students to numerical control part programming. Discussed in the first section are the impact of numerical control, training efforts, numerical control in established programs, related information for drafting, and the Cartesian Coordinate System and dimensioning…

SEMTAP (Serpentine End Match TApe program): The Easy Way to Program Your Numerically Controlled Router for the Production of SEM Joints

Treesearch

Ronald E. Coleman

1977-01-01

SEMTAP (Serpentine End Match TApe Program) is an easy and inexpensive method of programing a numerically controlled router for the manufacture of SEM (Serpentine End Matching) joints. The SEMTAP computer program allows the user to issue commands that will accurately direct a numerically controlled router along any SEM path. The user need not be a computer programer to...

Industrial Technology Modernization Program. Project 32. Factory Vision. Phase 2

DTIC Science & Technology

1988-04-01

instructions for the PWA’s, generating the numerical control (NC) program instructions for factory assembly equipment, controlling the process... generating the numerical control (NC) program instructions for factory assembly equipment, controlling the production process instructions and NC... Assembly Operations the "Create Production Process Program" will automatically generate a sequence of graphics pages (in paper mode), or graphics screens

Lessons Learned from the Hubble Space Telescope (HST) Contamination Control Program

NASA Technical Reports Server (NTRS)

Hansen, Patricia A.; Townsend, Jacqueline A.; Hedgeland, Randy J.

2004-01-01

Over the past two decades, the Hubble Space Telescope (HST) Contamination Control Program has evolved from a ground-based integration program to a space-based science-sustaining program. The contamination controls from the new-generation Scientific Instruments and Orbital Replacement Units were incorporated into the HST Contamination Control Program to maintain scientific capability over the life of the telescope. Long-term on-orbit scientific data has shown that these contamination controls implemented for the instruments, Servicing Mission activities (Orbiter, Astronauts, and mission), and on-orbit operations successfully protected the HST &om contamination and the instruments from self-contamination.

Lessons Learned from the Hubble Space Telescope (HST) Contamination Control Program

NASA Technical Reports Server (NTRS)

Hansen, Patricia A.; Townsend, Jacqueline A.; Hedgeland, Randy J.

2004-01-01

Over the past two decades, the Hubble Space Telescope (HST) Contamination Control Program has evolved from a ground-based integration program to a space-based science-sustaining program. The contamination controls from the new-generation Scientific Instruments and Orbital Replacement Units were incorporated into the HST Contamination Control Program to maintain scientific capability over the life of the telescope. Long-term on-orbit scientific data has shown that these contamination controls implemented for the instruments, Servicing Mission activities (Orbiter, Astronauts, and mission), and on-orbit operations successfully protected the HST from contamination and the instruments from self-contamination.

Controls-Structures Interaction (CSI) technology program summary. Earth orbiting platforms program area of the space platforms technology program

NASA Technical Reports Server (NTRS)

Newsom, Jerry R.

1991-01-01

Control-Structures Interaction (CSI) technology embraces the understanding of the interaction between the spacecraft structure and the control system, and the creation and validation of concepts, techniques, and tools, for enabling the interdisciplinary design of an integrated structure and control system, rather than the integration of a structural design and a control system design. The goal of this program is to develop validated CSI technology for integrated design/analysis and qualification of large flexible space systems and precision space structures. A description of the CSI technology program is presented.

Qualitative evaluation and economic estimates of an infection control champions program.

PubMed

Lloyd-Smith, Elisa; Curtin, Jim; Gilbart, Wayne; Romney, Marc G

2014-12-01

In many North American hospitals, conventional infection control operational models often struggle to provide sufficient support to frontline health care workers. The objective of this study was to describe a sustainable infection control champion (ICC) program based on findings from focus groups. A distributed model of infection control was established by placing infection prevention and control-trained ICCs in 3 Canadian hospitals for a period of 12 months. Subsequently, semistructured focus groups were conducted to describe overall feasibility and impeding and critical factors affecting sustainability. An economic estimate of the ICC program compared with the cost of hiring a new infection control practitioner was also calculated. Focus group participants considered the program feasible. Barriers included lack of time and staff turnover. Themes critical for the successful implementation of an ICC program included defined ICC roles and goals, adequate support and resources for the ICC, engagement with all levels of staff, flexible structure, and program evaluation. The cost per bed of the ICC program was less than the cost per bed of hiring a new infection control practitioner. A distributed model of providing infection prevention and control services may have benefit when hospital infection control teams are underresourced, as is often the case. Several key factors are needed for the successful implementation of an ICC program. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Controlled Substance Lock-In Programs: Examining An Unintended Consequence Of A Prescription Drug Abuse Policy.

PubMed

Roberts, Andrew W; Farley, Joel F; Holmes, G Mark; Oramasionwu, Christine U; Ringwalt, Chris; Sleath, Betsy; Skinner, Asheley C

2016-10-01

Controlled substance lock-in programs are garnering increased attention from payers and policy makers seeking to combat the epidemic of opioid misuse. These programs require high-risk patients to visit a single prescriber and pharmacy for coverage of controlled substance medication services. Despite high prevalence of the programs in Medicaid, we know little about their effects on patients' behavior and outcomes aside from reducing controlled substance-related claims. Our study was the first rigorous investigation of lock-in programs' effects on out-of-pocket controlled substance prescription fills, which circumvent the programs' restrictions and mitigate their potential public health benefits. We linked claims data and prescription drug monitoring program data for the period 2009-12 for 1,647 enrollees in North Carolina Medicaid's lock-in program and found that enrollment was associated with a roughly fourfold increase in the likelihood and frequency of out-of-pocket controlled substance prescription fills. This finding illuminates weaknesses of lock-in programs and highlights the need for further scrutiny of the appropriate role, optimal design, and potential unintended consequences of the programs as tools to prevent opioid abuse. Project HOPE—The People-to-People Health Foundation, Inc.

Regulatory considerations of occupational tuberculosis control.

PubMed

McDiarmid, M A; Gillen, N A; Hathon, L

1994-01-01

The authors argue that the classic hierarchy of industrial hygiene controls may be successfully used to control TB. Various elements of hygiene control programs reviewed here include TB exposure control programs, identification and isolation of patients, respiratory isolation, local source capture ventilation, laboratory procedures, employee surveillance programs, reporting of occupational illnesses, labeling requirements, and respiratory protection.

A real-time digital program for estimating aircraft stability and control parameters from flight test data by using the maximum likelihood method

NASA Technical Reports Server (NTRS)

Grove, R. D.; Mayhew, S. C.

1973-01-01

A computer program (Langley program C1123) has been developed for estimating aircraft stability and control parameters from flight test data. These parameters are estimated by the maximum likelihood estimation procedure implemented on a real-time digital simulation system, which uses the Control Data 6600 computer. This system allows the investigator to interact with the program in order to obtain satisfactory results. Part of this system, the control and display capabilities, is described for this program. This report also describes the computer program by presenting the program variables, subroutines, flow charts, listings, and operational features. Program usage is demonstrated with a test case using pseudo or simulated flight data.

Effects of Different Loci of Instructional Control on Students' Metacognition and Cognition: Learner vs. Program Control.

ERIC Educational Resources Information Center

Lee, Miheon J.

This study of 24 third-grade students learning Logo had 3 major research goals: (1) to compare the effects of learner control with those of program control on students' metacognition, knowledge acquisition, and knowledge application, with total subjects; (2) to extend the comparison between learner control and program control by classifying the…

Research Program for Vibration Control in Structures

NASA Technical Reports Server (NTRS)

Mingori, D. L.; Gibson, J. S.

1986-01-01

Purpose of program to apply control theory to large space structures (LSS's) and design practical compensator for suppressing vibration. Program models LSS as distributed system. Control theory applied to produce compensator described by functional gains and transfer functions. Used for comparison of robustness of low- and high-order compensators that control surface vibrations of realistic wrap-rib antenna. Program written in FORTRAN for batch execution.

7 CFR 58.141 - Alternate quality control program.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Alternate quality control program. 58.141 Section 58... Service 1 Quality Specifications for Raw Milk § 58.141 Alternate quality control program. When a plant has in operation an acceptable quality program, at the producer level, which is approved by the...

42 CFR 456.3 - Statewide surveillance and utilization control program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Statewide surveillance and utilization control... § 456.3 Statewide surveillance and utilization control program. The Medicaid agency must implement a statewide surveillance and utilization control program that— (a) Safeguards against unnecessary or...

42 CFR 456.3 - Statewide surveillance and utilization control program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Statewide surveillance and utilization control... § 456.3 Statewide surveillance and utilization control program. The Medicaid agency must implement a statewide surveillance and utilization control program that— (a) Safeguards against unnecessary or...

42 CFR 456.3 - Statewide surveillance and utilization control program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Statewide surveillance and utilization control... § 456.3 Statewide surveillance and utilization control program. The Medicaid agency must implement a statewide surveillance and utilization control program that— (a) Safeguards against unnecessary or...

42 CFR 456.3 - Statewide surveillance and utilization control program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Statewide surveillance and utilization control... § 456.3 Statewide surveillance and utilization control program. The Medicaid agency must implement a statewide surveillance and utilization control program that— (a) Safeguards against unnecessary or...

42 CFR 456.3 - Statewide surveillance and utilization control program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Statewide surveillance and utilization control... § 456.3 Statewide surveillance and utilization control program. The Medicaid agency must implement a statewide surveillance and utilization control program that— (a) Safeguards against unnecessary or...

[Effects of a Customized Birth Control Program for Married Immigrant Postpartum Mothers].

PubMed

Kim, So Young; Choi, So Young

2016-12-01

This study was conducted to develop a customized birth control program and identify its effects on attitude, subjective norm, behavioral control, intention, and behavior of contraception among immigrant postpartum mothers. In this experimental study, Vietnamese, Filipino or Cambodian married immigrant postpartum mothers were recruited. They were assigned to the experiment group (n=21) or control group (n=21). The customized birth control program was provided to the experimental group for 4 weeks. The experimental group showed a significant increase in the score of attitude, subjective norm, behavioral control, intention, and behavior of contraception. Findings in this study indicate that the customized postpartum birth control program, a systematic and integrative intervention program composed of customized health education, counseling and telephone monitoring, is able to provide effective planning for postpartum health promotion and birth control behavior practice in married immigrant women.

Microprocessor control system for 200-kilowatt Mod-OA wind turbines

NASA Technical Reports Server (NTRS)

Nyland, T. W.; Birchenough, A. G.

1982-01-01

The microprocessor system and program used to control the operation of the 200-kW Mod-OA wind turbines is described. The system is programmed to begin startup and shutdown sequences automatically and to control yaw motion. Rotor speed and power output are controlled with integral and proportional control of the blade pitch angle. Included in the report are a description of the hardware and a discussion of the software programming technique. A listing of the PL/M software program is given.

Government-to-private sector energy programs: Identification of common elements leading to successful implementation

NASA Astrophysics Data System (ADS)

Stockton, Keith M.

This dissertation examines six distinct government energy programs implemented in the United States during the last three decades. A common element within these programs is an attempt by government to drive commercialization of energy technologies leading to changes in energy production or consumptive behavior. We seek to understand the factors that lead to success or failure of these programs with two goals in mind. The first is theoretical in that we test a hypothesis that market-based energy programs have substantially higher success rates than command-and-control programs. The second goal is operational in nature, in which we desire to identify common factors within energy programs that lead either to program success or to failure. We investigate and evaluate three market-based and three command-and-control energy programs. The market-based programs include the federal Corporate Average Fuel Economy and Sulfur Dioxide Emissions Control programs as well as Colorado's Amendment 37. The command-and-control programs include the federal Synthetic Fuels Corporation and Corn Based Ethanol programs as well as Colorado's Solar Electric Power program. We conduct the analysis of each program based on composite methodology derived from leading academics within the Policy Sciences. From our research findings, we conclude that both market-based and command-and-control programs can achieve their legislative goals and objectives, resulting in permanent changes in energy production or consumptive behavior. However, we also find that the economic efficiency is the differentiator between market-based and command-and-control programs. Market-based programs, because of the inherent flexibility, allow participants to react to changing economic and/or technical conditions. In contrast, command-and-control programs lack such flexibility and often result in economic inefficiency when economic conditions change. The financial incentives incorporated in the three command-and-control programs we examined also create market distortions that both limit the flexibility of private markets to adjust to changing economic conditions and discourage the adoption of competing technologies. We conclude our research by recommending that future policy makers maximize the range of methods availability to the private sector to meet legislative goals and limit the use of financial incentives. With these measures, energy programs may achieve higher levels of success by reaching their goals with maximum economic efficiency and minimal negative unanticipated consequences.

A real-time digital computer program for the simulation of automatic spacecraft reentries

NASA Technical Reports Server (NTRS)

Kaylor, J. T.; Powell, L. F.; Powell, R. W.

1977-01-01

The automatic reentry flight dynamics simulator, a nonlinear, six-degree-of-freedom simulation, digital computer program, has been developed. The program includes a rotating, oblate earth model for accurate navigation calculations and contains adjustable gains on the aerodynamic stability and control parameters. This program uses a real-time simulation system and is designed to examine entries of vehicles which have constant mass properties whose attitudes are controlled by both aerodynamic surfaces and reaction control thrusters, and which have automatic guidance and control systems. The program has been used to study the space shuttle orbiter entry. This report includes descriptions of the equations of motion used, the control and guidance schemes that were implemented, the program flow and operation, and the hardware involved.

Quality control education in the community college

NASA Technical Reports Server (NTRS)

Greene, J. Griffen; Wilson, Steve

1966-01-01

This paper describes the Quality Control Program at Daytona Beach Junior College, including course descriptions. The program in quality control required communication between the college and the American Society for Quality Control (ASQC). The college has machinery established for certification of the learning process, and the society has the source of teachers who are competent in the technical field and who are the employers of the educational products. The associate degree for quality control does not have a fixed program, which can serve all needs, any more than all engineering degrees have identical programs. The main ideas which would be common to all quality control programs are the concept of economic control of a repetitive process and the concept of developing individual potentialities into individuals who are needed and productive.

Improving Control of Two Motor Controllers

NASA Technical Reports Server (NTRS)

Toland, Ronald W.

2004-01-01

A computer program controls motors that drive translation stages in a metrology system that consists of a pair of two-axis cathetometers. This program is specific to Compumotor Gemini (or equivalent) motors and the Compumotor 6K-series (or equivalent) motor controller. Relative to the software supplied with the controller, this program affords more capabilities and is easier to use. Written as a Virtual Instrument in the LabVIEW software system, the program presents an imitation control panel that the user can manipulate by use of a keyboard and mouse. There are three modes of operation: command, movement, and joystick. In command mode, single commands are sent to the controller for troubleshooting. In movement mode, distance, speed, and/or acceleration commands are sent to the controller. Position readouts from the motors and from position encoders on the translation stages are displayed in marked fields. At any time, the position readouts can be recorded in a file named by the user. In joystick mode, the program yields control of the motors to a joystick. The program sends commands to, and receives data from, the controller via a serial cable connection, using the serial-communication portion of the software supplied with the controller.

System For Research On Multiple-Arm Robots

NASA Technical Reports Server (NTRS)

Backes, Paul G.; Hayati, Samad; Tso, Kam S.; Hayward, Vincent

1991-01-01

Kali system of computer programs and equipment provides environment for research on distributed programming and distributed control of coordinated-multiple-arm robots. Suitable for telerobotics research involving sensing and execution of low level tasks. Software and configuration of hardware designed flexible so system modified easily to test various concepts in control and programming of robots, including multiple-arm control, redundant-arm control, shared control, traded control, force control, force/position hybrid control, design and integration of sensors, teleoperation, task-space description and control, methods of adaptive control, control of flexible arms, and human factors.

18 CFR 12.40 - Quality control programs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Quality control... PROJECT WORKS Other Responsibilities of Applicant or Licensee § 12.40 Quality control programs. (a... meeting any requirements or standards set by the Regional Engineer. If a quality control program is...

18 CFR 12.40 - Quality control programs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Quality control... PROJECT WORKS Other Responsibilities of Applicant or Licensee § 12.40 Quality control programs. (a... meeting any requirements or standards set by the Regional Engineer. If a quality control program is...

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

[Role of the independent microbiology laboratory in supporting infection control programs in small to mid-sized hospitals].

PubMed

Yanagisawa, Hideji

2009-05-01

With the revision of the Medical Service Law in 2006 by the Japanese Ministry of Health, Labour and Welfare (MHLW), all healthcare institutions are now required to implement a healthcare risk management program including infection control program. At a national level, an infection control surveillance program (JANIS) was implemented in July 2007. Regular weekly, monthly, and yearly infection control surveillance reports from independent microbiology laboratories can make significant contributions to infection control programs in small to mid-sized hospitals; furthermore, such programs are consistent with the framework of the MHLW's objective of strengthening risk management in healthcare institutions. Against the backdrop of current efforts to improve risk management, independent laboratories can make a significant contribution. Independent laboratories must play a role beyond merely receiving and processing specimens for microbiological examination. In addition to generating results for patients, hospital epidemiological data that contribute to local infection control programs must be a value-added component of the service. A major obstacle for independent laboratories to make a significant contribution to risk management is the current reimbursement system, which makes it economically impossible for independent laboratories to support infection control programs in healthcare institutions.

Propulsion/flight control integration technology (PROFIT) software system definition

NASA Technical Reports Server (NTRS)

Carlin, C. M.; Hastings, W. J.

1978-01-01

The Propulsion Flight Control Integration Technology (PROFIT) program is designed to develop a flying testbed dedicated to controls research. The control software for PROFIT is defined. Maximum flexibility, needed for long term use of the flight facility, is achieved through a modular design. The Host program, processes inputs from the telemetry uplink, aircraft central computer, cockpit computer control and plant sensors to form an input data base for use by the control algorithms. The control algorithms, programmed as application modules, process the input data to generate an output data base. The Host program formats the data for output to the telemetry downlink, the cockpit computer control, and the control effectors. Two applications modules are defined - the bill of materials F-100 engine control and the bill of materials F-15 inlet control.

Propulsion system-flight control integration-flight evaluation and technology transition

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Gilyard, Glenn B.; Myers, Lawrence P.

1990-01-01

Integration of propulsion and flight control systems and their optimization offering significant performance improvement are assessed. In particular, research programs conducted by NASA on flight control systems and propulsion system-flight control interactions on the YF-12 and F-15 aircraft are addressed; these programs have demonstrated increased thrust, reduced fuel consumption, increased engine life, and improved aircraft performance. Focus is placed on altitude control, speed-Mach control, integrated controller design, as well as flight control systems and digital electronic engine control. A highly integrated digital electronic control program is analyzed and compared with a performance seeking control program. It is shown that the flight evaluation and demonstration of these technologies have been a key part in the transition of the concepts to production and operational use on a timely basis.

[Filariasis control: entry point for other helminthiasis control programs?].

PubMed

Boussinesq, M

2006-08-01

Filariasis control programs are based on a decentralized drug distribution strategy known as "community-directed". This strategy could also be applied to the control of schistosomiasis and intestinal nematode infections. Integration of these control programs could be highly cost-effective. However, as a prerequisite for integration, it would be necessary to identify zones where these helminthic infections co-exist, specify the population categories that should receive each medication (ivermectin, albendazole, mebendazole, and praziquantel), check that combined administration of these drugs is safe and ensure that an integrated program would have no detrimental effect on the health care system and on the efficacy of ongoing programs.

48 CFR 819.7112 - Internal controls.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Internal controls. 819.7112 Section 819.7112 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS VA Mentor-Protégé Program 819.7112 Internal controls. (a) OSDBU will oversee the Program and will work...

Energy Efficient Engine: Control system preliminary definition report

NASA Technical Reports Server (NTRS)

Howe, David C.

1986-01-01

The object of the Control Preliminary Definition Program was to define a preliminary control system concept as a part of the Energy Efficient Engine program. The program was limited to a conceptual definition of a full authority digital electronic control system. System requirements were determined and a control system was conceptually defined to these requirements. Areas requiring technological development were identified and a plan was established for implementing the identified technological features, including a control technology demonstration. A significant element of this program was a study of the potential benefits of closed-loop active clearance control, along with laboratory tests of candidate clearance sensor elements for a closed loop system.

Daylight control system device and method

DOEpatents

Paton, John Douglas

2007-03-13

A system and device for and a method of programming and controlling light fixtures is disclosed. A system in accordance with the present invention includes a stationary controller unit that is electrically coupled to the light fixtures. The stationary controller unit is configured to be remotely programmed with a portable commissioning device to automatically control the lights fixtures. The stationary controller unit and the portable commissioning device include light sensors, micro-computers and transceivers for measuring light levels, running programs, storing data and transmitting data between the stationary controller unit and the portable commissioning device. In operation, target light levels selected with the portable commissioning device and the controller unit is remotely programmed to automatically maintain the target level.

Daylight control system, device and method

DOEpatents

Paton, John Douglas

2012-08-28

A system and device for and a method of programming and controlling light fixtures is disclosed. A system in accordance with the present invention includes a stationary controller unit that is electrically coupled to the light fixtures. The stationary controller unit is configured to be remotely programmed with a portable commissioning device to automatically control the lights fixtures. The stationary controller unit and the portable commissioning device include light sensors, micro-computers and transceivers for measuring light levels, running programs, storing data and transmitting data between the stationary controller unit and the portable commissioning device. In operation, target light levels selected with the portable commissioning device and the controller unit is remotely programmed to automatically maintain the target level.

Daylight control system device and method

DOEpatents

Paton, John Douglas

2009-12-01

A system and device for and a method of programming and controlling light fixtures is disclosed. A system in accordance with the present invention includes a stationary controller unit that is electrically coupled to the light fixtures. The stationary controller unit is configured to be remotely programmed with a portable commissioning device to automatically control the lights fixtures. The stationary controller unit and the portable commissioning device include light sensors, micro-computers and transceivers for measuring light levels, running programs, storing data and transmitting data between the stationary controller unit and the portable commissioning device. In operation, target light levels selected with the portable commissioning device and the controller unit is remotely programmed to automatically maintain the target level.

A Clustered Randomized Controlled Trial of the Positive Prevention PLUS Adolescent Pregnancy Prevention Program.

PubMed

LaChausse, Robert G

2016-09-01

To determine the impact of Positive Prevention PLUS, a school-based adolescent pregnancy prevention program on delaying sexual intercourse, birth control use, and pregnancy. I randomly assigned a diverse sample of ninth grade students in 21 suburban public high schools in California into treatment (n = 2483) and control (n = 1784) groups that participated in a clustered randomized controlled trial. Between October 2013 and May 2014, participants completed baseline and 6-month follow-up surveys regarding sexual behavior and pregnancy. Participants in the treatment group were offered Positive Prevention PLUS, an 11-lesson adolescent pregnancy prevention program. The program had statistically significant impacts on delaying sexual intercourse and increasing the use of birth control. However, I detected no program effect on pregnancy rates at 6-month follow-up. The Positive Prevention PLUS program demonstrated positive impacts on adolescent sexual behavior. This suggests that programs that focus on having students practice risk reduction skills may delay sexual activity and increase birth control use.

47 CFR 76.1001 - Unfair practices generally.

Code of Federal Regulations, 2012 CFR

2012-10-01

... control with a cable operator or cable operators, satellite cable programming vendor or vendors in which a... under common control with, such terrestrial cable programming vendor shall be deemed responsible for... programming vendor is wholly owned by, controlled by, or under common control with a cable operator or cable...

47 CFR 76.1001 - Unfair practices generally.

Code of Federal Regulations, 2014 CFR

2014-10-01

... control with a cable operator or cable operators, satellite cable programming vendor or vendors in which a... under common control with, such terrestrial cable programming vendor shall be deemed responsible for... programming vendor is wholly owned by, controlled by, or under common control with a cable operator or cable...

47 CFR 76.1001 - Unfair practices generally.

Code of Federal Regulations, 2013 CFR

2013-10-01

... control with a cable operator or cable operators, satellite cable programming vendor or vendors in which a... under common control with, such terrestrial cable programming vendor shall be deemed responsible for... programming vendor is wholly owned by, controlled by, or under common control with a cable operator or cable...

Effect of the California Tobacco Control Program on Personal Health Care Expenditures

PubMed Central

Lightwood, James M; Dinno, Alexis; Glantz, Stanton A

2008-01-01

Background Large state tobacco control programs have been shown to reduce smoking and would be expected to affect health care costs. We investigate the effect of California's large-scale tobacco control program on aggregate personal health care expenditures in the state. Methods and Findings Cointegrating regressions were used to predict (1) the difference in per capita cigarette consumption between California and 38 control states as a function of the difference in cumulative expenditures of the California and control state tobacco control programs, and (2) the relationship between the difference in cigarette consumption and the difference in per capita personal health expenditures between the control states and California between 1980 and 2004. Between 1989 (when it started) and 2004, the California program was associated with $86 billion (2004 US dollars) (95% confidence interval [CI] $28 billion to $151 billion) lower health care expenditures than would have been expected without the program. This reduction grew over time, reaching 7.3% (95% CI 2.7%–12.1%) of total health care expenditures in 2004. Conclusions A strong tobacco control program is not only associated with reduced smoking, but also with reductions in health care expenditures. PMID:18752344

Operators manual for the magnetograph program (section 2)

NASA Technical Reports Server (NTRS)

November, L.; Title, A. M.

1974-01-01

This manual for use of the magnetograph program describes: (1) black box use of the programs; (2) the magtape data formats used; (3) the adjustable control parameters in the program; and (4) the algorithms. With no adjustments on the control parameters this program may be used purely as a black box. For optimal use, however, the control parameters may be varied. The magtape data formats are of use in adopting other programs to look at raw data or final magnetograph data.

Gesture-Controlled Interface for Contactless Control of Various Computer Programs with a Hooking-Based Keyboard and Mouse-Mapping Technique in the Operating Room

PubMed Central

Park, Ben Joonyeon; Jang, Taekjin; Choi, Jong Woo; Kim, Namkug

2016-01-01

We developed a contactless interface that exploits hand gestures to effectively control medical images in the operating room. We developed an in-house program called GestureHook that exploits message hooking techniques to convert gestures into specific functions. For quantitative evaluation of this program, we used gestures to control images of a dynamic biliary CT study and compared the results with those of a mouse (8.54 ± 1.77 s to 5.29 ± 1.00 s; p < 0.001) and measured the recognition rates of specific gestures and the success rates of tasks based on clinical scenarios. For clinical applications, this program was set up in the operating room to browse images for plastic surgery. A surgeon browsed images from three different programs: CT images from a PACS program, volume-rendered images from a 3D PACS program, and surgical planning photographs from a basic image viewing program. All programs could be seamlessly controlled by gestures and motions. This approach can control all operating room programs without source code modification and provide surgeons with a new way to safely browse through images and easily switch applications during surgical procedures. PMID:26981146

Gesture-Controlled Interface for Contactless Control of Various Computer Programs with a Hooking-Based Keyboard and Mouse-Mapping Technique in the Operating Room.

PubMed

Park, Ben Joonyeon; Jang, Taekjin; Choi, Jong Woo; Kim, Namkug

2016-01-01

We developed a contactless interface that exploits hand gestures to effectively control medical images in the operating room. We developed an in-house program called GestureHook that exploits message hooking techniques to convert gestures into specific functions. For quantitative evaluation of this program, we used gestures to control images of a dynamic biliary CT study and compared the results with those of a mouse (8.54 ± 1.77 s to 5.29 ± 1.00 s; p < 0.001) and measured the recognition rates of specific gestures and the success rates of tasks based on clinical scenarios. For clinical applications, this program was set up in the operating room to browse images for plastic surgery. A surgeon browsed images from three different programs: CT images from a PACS program, volume-rendered images from a 3D PACS program, and surgical planning photographs from a basic image viewing program. All programs could be seamlessly controlled by gestures and motions. This approach can control all operating room programs without source code modification and provide surgeons with a new way to safely browse through images and easily switch applications during surgical procedures.

Model-based control strategies for systems with constraints of the program type

NASA Astrophysics Data System (ADS)

Jarzębowska, Elżbieta

2006-08-01

The paper presents a model-based tracking control strategy for constrained mechanical systems. Constraints we consider can be material and non-material ones referred to as program constraints. The program constraint equations represent tasks put upon system motions and they can be differential equations of orders higher than one or two, and be non-integrable. The tracking control strategy relies upon two dynamic models: a reference model, which is a dynamic model of a system with arbitrary order differential constraints and a dynamic control model. The reference model serves as a motion planner, which generates inputs to the dynamic control model. It is based upon a generalized program motion equations (GPME) method. The method enables to combine material and program constraints and merge them both into the motion equations. Lagrange's equations with multipliers are the peculiar case of the GPME, since they can be applied to systems with constraints of first orders. Our tracking strategy referred to as a model reference program motion tracking control strategy enables tracking of any program motion predefined by the program constraints. It extends the "trajectory tracking" to the "program motion tracking". We also demonstrate that our tracking strategy can be extended to a hybrid program motion/force tracking.

LABORATORY PROCESS CONTROLLER USING NATURAL LANGUAGE COMMANDS FROM A PERSONAL COMPUTER

NASA Technical Reports Server (NTRS)

Will, H.

1994-01-01

The complex environment of the typical research laboratory requires flexible process control. This program provides natural language process control from an IBM PC or compatible machine. Sometimes process control schedules require changes frequently, even several times per day. These changes may include adding, deleting, and rearranging steps in a process. This program sets up a process control system that can either run without an operator, or be run by workers with limited programming skills. The software system includes three programs. Two of the programs, written in FORTRAN77, record data and control research processes. The third program, written in Pascal, generates the FORTRAN subroutines used by the other two programs to identify the user commands with the user-written device drivers. The software system also includes an input data set which allows the user to define the user commands which are to be executed by the computer. To set the system up the operator writes device driver routines for all of the controlled devices. Once set up, this system requires only an input file containing natural language command lines which tell the system what to do and when to do it. The operator can make up custom commands for operating and taking data from external research equipment at any time of the day or night without the operator in attendance. This process control system requires a personal computer operating under MS-DOS with suitable hardware interfaces to all controlled devices. The program requires a FORTRAN77 compiler and user-written device drivers. This program was developed in 1989 and has a memory requirement of about 62 Kbytes.

A novel, helminth-derived immunostimulant enhances human recall responses to hepatitis C virus and tetanus toxoid and is dependent on CD56+ cells for its action.

PubMed

MacDonald, A J; Libri, N A; Lustigman, S; Barker, S J; Whelan, M A; Semper, A E; Rosenberg, W M

2008-05-01

We have described previously an immunostimulant derived from Onchocerca volvulus, the helminth parasite that causes onchocerciasis. Recombinant O. volvulus activation-associated secreted protein-1 (rOv-ASP-1) was a potent adjuvant for antibody and cellular responses to protein, polypeptide and small peptide antigens. Our aims were to determine whether rOv-ASP-1 is immunostimulatory for human peripheral blood mononuclear cells (PBMC) and, if so, whether it could augment cellular responses against human pathogen antigens in vitro. Cytokines from rOv-ASP-1-stimulated human PBMC were measured by a fluorescence activated cell sorter-based multiplex assay. Recall responses of normal healthy donor (NHD) and chronic hepatitis C virus (c-HCV)-infected patient PBMC to tetanus toxoid (TT) or HCV core (HCVco) antigen, respectively, were measured by interferon-gamma enzyme-linked immunospot assays. Interferon-gamma was the predominant cytokine induced by rOv-ASP-1. 77.3% of NHD anti-TT and 88.9% of c-HCV anti-HCVco responses were enhanced by rOv-ASP-1. The immunostimulant effect was dependent upon contact between CD56+ and CD56- fractions of PBMC. We have described a helminth-derived protein that can act as an immunostimulant for human recall responses in vitro to TT and, perhaps more importantly, HCV antigens in patients with chronic HCV infection. Our longer-term goal would be to boost anti-viral responses in chronic infections such as HCV.

The Canadian effort to prevent and control hypertension: can other countries adopt Canadian strategies?

PubMed

Campbell, Norm R C; Sheldon, Tobe

2010-07-01

To indicate the key elements of current Canadian programs to treat and control hypertension. In the early 1990s Canada had a hypertension treatment and control rate of 13%. A Canadian strategy to prevent and control hypertension was developed and a coalition of national organizations and volunteers formed to develop increasingly extensive programs. The Canadian effort was largely based on annually updated hypertension management recommendations, an integrated and extensive hypertension knowledge translation program and an increasingly comprehensive outcomes assessment program. After the start of the annual process in 1999, there were very large increases in diagnosis and hypertension treatment coupled with dropping rates of cardiovascular disease. More recent initiatives include an extensive education program for the public and people with hypertension, a program to reduce dietary salt and a funded leadership position. The treatment and control rate increased to 66% when last assessed (2007-2009). The study describes important aspects of the Canadian hypertension management programs to aid those wishing to develop similar programs. Many of the programs could be fully or partially implemented by other countries.

42 CFR 431.810 - Basic elements of the Medicaid eligibility quality control (MEQC) program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Basic elements of the Medicaid eligibility quality control (MEQC) program. 431.810 Section 431.810 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... GENERAL ADMINISTRATION Quality Control Medicaid Eligibility Quality Control (meqc) Program § 431.810 Basic...

48 CFR 719.273-10 - Internal controls.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Internal controls. 719.273...égé Program 719.273-10 Internal controls. (a) OSDBU will oversee the Program and will work in... objectives. OSDBU will establish internal controls as checks and balances applicable to the Program. These...

48 CFR 719.273-10 - Internal controls.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Internal controls. 719.273...égé Program 719.273-10 Internal controls. (a) OSDBU will oversee the Program and will work in... objectives. OSDBU will establish internal controls as checks and balances applicable to the Program. These...

48 CFR 719.273-10 - Internal controls.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Internal controls. 719.273...égé Program 719.273-10 Internal controls. (a) OSDBU will oversee the Program and will work in... objectives. OSDBU will establish internal controls as checks and balances applicable to the Program. These...

48 CFR 719.273-10 - Internal controls.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Internal controls. 719.273...égé Program 719.273-10 Internal controls. (a) OSDBU will oversee the Program and will work in... objectives. OSDBU will establish internal controls as checks and balances applicable to the Program. These...

Control Robotics Programming Technology. Technology Learning Activity. Teacher Edition.

ERIC Educational Resources Information Center

Oklahoma State Dept. of Vocational and Technical Education, Stillwater. Curriculum and Instructional Materials Center.

This Technology Learning Activity (TLA) for control robotics programming technology in grades 6-10 is designed to teach students to construct and program computer-controlled devices using a LEGO DACTA set and computer interface and to help them understand how control technology and robotics affect them and their lifestyle. The suggested time for…

Controlling Laboratory Processes From A Personal Computer

NASA Technical Reports Server (NTRS)

Will, H.; Mackin, M. A.

1991-01-01

Computer program provides natural-language process control from IBM PC or compatible computer. Sets up process-control system that either runs without operator or run by workers who have limited programming skills. Includes three smaller programs. Two of them, written in FORTRAN 77, record data and control research processes. Third program, written in Pascal, generates FORTRAN subroutines used by other two programs to identify user commands with device-driving routines written by user. Also includes set of input data allowing user to define user commands to be executed by computer. Requires personal computer operating under MS-DOS with suitable hardware interfaces to all controlled devices. Also requires FORTRAN 77 compiler and device drivers written by user.

A user's guide to the Flexible Spacecraft Dynamics and Control Program

NASA Technical Reports Server (NTRS)

Fedor, J. V.

1984-01-01

A guide to the use of the Flexible Spacecraft Dynamics Program (FSD) is presented covering input requirements, control words, orbit generation, spacecraft description and simulation options, and output definition. The program can be used in dynamics and control analysis as well as in orbit support of deployment and control of spacecraft. The program is applicable to inertially oriented spinning, Earth oriented or gravity gradient stabilized spacecraft. Internal and external environmental effects can be simulated.

An Economic Analysis of USDA Erosion Control Programs: A New Perspective. Agricultural Economic Report No. 560.

ERIC Educational Resources Information Center

Strohbehn, Roger, Ed.

A study analyzed the total (public and private) economic costs and benefits of three U.S. Department of Agriculture erosion control programs. These were the Conservation Technical Assistance Program, Great Plains Conservation Program, and Agricultural Conservation Program. Significant efforts at funding for current programs were directed to…

41 CFR 102-33.135 - Do we have to follow the direction in OMB Circular A-123, “Management Accountability and Control...

Code of Federal Regulations, 2012 CFR

2012-01-01

... management controls for our aviation program? 102-33.135 Section 102-33.135 Public Contracts and Property... Control,” June 21, 1995, for establishing management controls for our aviation program? Yes, you must... establishing management controls for your aviation program. (See Note to § 102-33.70.) The circular requires...

41 CFR 102-33.135 - Do we have to follow the direction in OMB Circular A-123, “Management Accountability and Control...

Code of Federal Regulations, 2011 CFR

2011-01-01

... management controls for our aviation program? 102-33.135 Section 102-33.135 Public Contracts and Property... Control,” June 21, 1995, for establishing management controls for our aviation program? Yes, you must... establishing management controls for your aviation program. (See Note to § 102-33.70.) The circular requires...

41 CFR 102-33.135 - Do we have to follow the direction in OMB Circular A-123, “Management Accountability and Control...

Code of Federal Regulations, 2010 CFR

2010-07-01

... management controls for our aviation program? 102-33.135 Section 102-33.135 Public Contracts and Property... Control,” June 21, 1995, for establishing management controls for our aviation program? Yes, you must... establishing management controls for your aviation program. (See Note to § 102-33.70.) The circular requires...

41 CFR 102-33.135 - Do we have to follow the direction in OMB Circular A-123, “Management Accountability and Control...

Code of Federal Regulations, 2014 CFR

2014-01-01

... management controls for our aviation program? 102-33.135 Section 102-33.135 Public Contracts and Property... Control,” June 21, 1995, for establishing management controls for our aviation program? Yes, you must... establishing management controls for your aviation program. (See Note to § 102-33.70.) The circular requires...

41 CFR 102-33.135 - Do we have to follow the direction in OMB Circular A-123, “Management Accountability and Control...

Code of Federal Regulations, 2013 CFR

2013-07-01

... management controls for our aviation program? 102-33.135 Section 102-33.135 Public Contracts and Property... Control,” June 21, 1995, for establishing management controls for our aviation program? Yes, you must... establishing management controls for your aviation program. (See Note to § 102-33.70.) The circular requires...

Cargo Movement Operations System (CMOS). Software Requirements Specification, Increment 1, Change 02

DTIC Science & Technology

1990-05-24

COMMENT: YES [ ] NO [ ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ CLOSED [ ] ORIGINATOR CONTROL NUMBER: SRS2-0002 PROGRAM OFFICE CONTROL NUMBER: DATA...ACCEPTS COMMENT: YES ( J NO [ ) COMMENT DISPOSITION: COMMENT STATUS: OPEN [ J CLOSED [ ] ORIGINATOR CONTROL NUMBER: SRS2-0003 PROGRAM OFFICE CONTROL...NO [ ] ERCI ACCEPTS COMMENT: YES [ ] NO ( ] COMMENT DISPOSITION: COMMENT STATUS: OPEN [ ] CLOSED [ J ORIGINATOR CONTROL NUMBER: SRS2-0004 PROGRAM

The History and Use of Cancer Registry Data by Public Health Cancer Control Programs in the United States

PubMed Central

White, Mary C.; Babcock, Frances; Hayes, Nikki S.; Mariotto, Angela B.; Wong, Faye L.; Kohler, Betsy A.; Weir, Hannah K.

2018-01-01

Because cancer registry data provide a census of cancer cases, registry data can be used to: 1) define and monitor cancer incidence at the local, state, and national levels; 2) investigate patterns of cancer treatment; and 3) evaluate the effectiveness of public health efforts to prevent cancer cases and improve cancer survival. The purpose of this article is to provide a broad overview of the history of cancer surveillance programs in the United States, and illustrate the expanding ways in which cancer surveillance data are being made available and contributing to cancer control programs. The article describes the building of the cancer registry infrastructure and the successful coordination of efforts among the 2 federal agencies that support cancer registry programs, the Centers for Disease Control and Prevention and the National Cancer Institute, and the North American Association of Central Cancer Registries. The major US cancer control programs also are described, including the National Comprehensive Cancer Control Program, the National Breast and Cervical Cancer Early Detection Program, and the Colorectal Cancer Control Program. This overview illustrates how cancer registry data can inform public health actions to reduce disparities in cancer outcomes and may be instructional for a variety of cancer control professionals in the United States and in other countries. PMID:29205307

On a program manifold's stability of one contour automatic control systems

NASA Astrophysics Data System (ADS)

Zumatov, S. S.

2017-12-01

Methodology of analysis of stability is expounded to the one contour systems automatic control feedback in the presence of non-linearities. The methodology is based on the use of the simplest mathematical models of the nonlinear controllable systems. Stability of program manifolds of one contour automatic control systems is investigated. The sufficient conditions of program manifold's absolute stability of one contour automatic control systems are obtained. The Hurwitz's angle of absolute stability was determined. The sufficient conditions of program manifold's absolute stability of control systems by the course of plane in the mode of autopilot are obtained by means Lyapunov's second method.

Financial Audit: Guaranteed Student Loan Program's Internal Controls and Structure Need Improvement. Report to the Congress.

ERIC Educational Resources Information Center

Wurtz, Donald R.; And Others

An evaluative study was done of the Department of Education's system of internal accounting controls over the Federal Family Education Loan Program, known as the guaranteed student loan program. The study evaluated internal control systems, the structure of the program with respect to the role of guaranty agencies, and the Department's ability to…

FINITE-STATE APPROXIMATIONS TO DENUMERABLE-STATE DYNAMIC PROGRAMS,

DTIC Science & Technology

AIR FORCE OPERATIONS, LOGISTICS), (*INVENTORY CONTROL, DYNAMIC PROGRAMMING), (*DYNAMIC PROGRAMMING, APPROXIMATION(MATHEMATICS)), INVENTORY CONTROL, DECISION MAKING, STOCHASTIC PROCESSES, GAME THEORY, ALGORITHMS, CONVERGENCE

33 CFR Appendix A to Part 273 - Aquatic Plant Control Program Legislative Authority

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Aquatic Plant Control Program... OF THE ARMY, DEPARTMENT OF DEFENSE AQUATIC PLANT CONTROL Pt. 273, App. A Appendix A to Part 273—Aquatic Plant Control Program Legislative Authority Section 104 of the Rivers and Harbors Act, approved 3...

33 CFR Appendix A to Part 273 - Aquatic Plant Control Program Legislative Authority

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Aquatic Plant Control Program... OF THE ARMY, DEPARTMENT OF DEFENSE AQUATIC PLANT CONTROL Pt. 273, App. A Appendix A to Part 273—Aquatic Plant Control Program Legislative Authority Section 104 of the Rivers and Harbors Act, approved 3...

[Application of multiple-attribute utility technology (MAUT) to decisions about a work-site stress-control intervention for public-sector office workers].

PubMed

Hagihara, Akihito; Tarumi, Kimio

2013-01-01

The reasons behind the establishment of particular health-promotion programs in community or work settings are often unclear, and such programs are rarely evaluated from a broad perspective after they are implemented. Thus, multiattribute utility technology (MAUT) was used to design a work-site stress-control program. The sample consisted of public-sector workers in B City in Japan. Stakeholders in the work-site stress-control program included employers (municipal authorities), employees (public workers), and healthcare personnel. Six goals and three strategies (i.e., personnel, self-care, and staff) related to stress-control programs were considered. The results showed that the self-care strategy received the highest score for overall utility (i.e., 96.2), and the overall-utility score for the remaining two strategies was approximately 70. The self-care strategy emerged as the most useful of the three strategies for developing a stress-control program in a target work place. The application of MAUT may be useful for developing an effective stress-control program in occupational settings.

Tank waste remediation system privatization infrastructure program, configuration management implementation plan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaus, P.S.

This Configuration Management Implementation Plan (CMIP) was developed to assist in managing systems, structures, and components (SSCS), to facilitate the effective control and statusing of changes to SSCS, and to ensure technical consistency between design, performance, and operational requirements. Its purpose is to describe the approach Privatization Infrastructure will take in implementing a configuration management program, to identify the Program`s products that need configuration management control, to determine the rigor of control, and to identify the mechanisms for that control.

Programming Support Library (PSL). Users Manual.

DTIC Science & Technology

1978-05-01

which provides the tools to organize, implement, and control computer program develop- ment. This involves the support of the actual programming process...provides the tools toorganize, implement, and control computer program development. The system is designed specifically to support top-down development...Structured Programming are finding increasing application in the computing community. Structured programs are, however, difficult to write in

A Comprehensive Approach to Management of Workplace and Environmental Noise at NASA Lewis Research Center

NASA Technical Reports Server (NTRS)

Cooper, Beth A.

1995-01-01

NASA Lewis Research Center is home to more than 100 experimental research testing facilities and laboratories, including large wind tunnels and engine test cells, which in combination create a varied and complex noise environment. Much of the equipment was manufactured prior to the enactment of legislation limiting product noise emissions or occupational noise exposure. Routine facility maintenance and associated construction also contributes to a noise exposure management responsibility which is equal in magnitude and scope to that of several small industrial companies. The Noise Program, centrally managed within the Office of Environmental Programs at LRC, maintains overall responsibility for hearing conservation, community noise control, and acoustical and noise control engineering. Centralized management of the LRC Noise Program facilitates the timely development and implementation of engineered noise control solutions for problems identified via either the Hearing Conservation of Community Noise Program. The key element of the Lewis Research Center Noise Program, Acoustical and Noise Control Engineering Services, is focused on developing solutions that permanently reduce employee and community noise exposure and maximize research productivity by reducing or eliminating administrative and operational controls and by improving the safety and comfort of the work environment. The Hearing Conservation Program provides noise exposure assessment, medical monitoring, and training for civil servant and contractor employees. The Community Noise Program aims to maintain the support of LRC's neighboring communities while enabling necessary research operations to accomplish their programmatic goals. Noise control engineering capability resides within the Noise Program. The noise control engineering, based on specific exposure limits, is a fundamental consideration throughout the design phase of new test facilities, labs, and office buildings. In summary, the Noise Program addresses hearing conservation, community noise control, and acoustical and noise control engineering.

Computer program CDCID: an automated quality control program using CDC update

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singer, G.L.; Aguilar, F.

1984-04-01

A computer program, CDCID, has been developed in coordination with a quality control program to provide a highly automated method of documenting changes to computer codes at EG and G Idaho, Inc. The method uses the standard CDC UPDATE program in such a manner that updates and their associated documentation are easily made and retrieved in various formats. The method allows each card image of a source program to point to the document which describes it, who created the card, and when it was created. The method described is applicable to the quality control of computer programs in general. Themore » computer program described is executable only on CDC computing systems, but the program could be modified and applied to any computing system with an adequate updating program.« less

Application of advanced control techniques to aircraft propulsion systems

NASA Technical Reports Server (NTRS)

Lehtinen, B.

1984-01-01

Two programs are described which involve the application of advanced control techniques to the design of engine control algorithms. Multivariable control theory is used in the F100 MVCS (multivariable control synthesis) program to design controls which coordinate the control inputs for improved engine performance. A systematic method for handling a complex control design task is given. Methods of analytical redundancy are aimed at increasing the control system reliability. The F100 DIA (detection, isolation, and accommodation) program, which investigates the uses of software to replace or augment hardware redundancy for certain critical engine sensor, is described.

23 CFR 637.207 - Quality assurance program.

Code of Federal Regulations, 2011 CFR

2011-04-01

... independent assurance (IA) program consisting of the following: (1) Acceptance program. (i) Each STD's... quality control samples. (C) The quality control sampling and testing is evaluated by an IA program. (iii... appropriate. See 23 CFR 635.413(e) for specific requirements. (2) The IA program shall evaluate the qualified...

Integrated digital flight-control system for the space shuttle orbiter

NASA Technical Reports Server (NTRS)

1973-01-01

The integrated digital flight control system is presented which provides rotational and translational control of the space shuttle orbiter in all phases of flight: from launch ascent through orbit to entry and touchdown, and during powered horizontal flights. The program provides a versatile control system structure while maintaining uniform communications with other programs, sensors, and control effectors by using an executive routine/functional subroutine format. The program reads all external variables at a single point, copies them into its dedicated storage, and then calls the required subroutines in the proper sequence. As a result, the flight control program is largely independent of other programs in the GN&C computer complex and is equally insensitive to the characteristics of the processor configuration. The integrated structure of the control system and the DFCS executive routine which embodies that structure are described along with the input and output. The specific estimation and control algorithms used in the various mission phases are given.

[Challenges and countermeasures of forestry schistosomiasis control programs in ecological priority of Yangtze River economic belt development].

PubMed

Ning, Su; Yong-Jie, Xu

2016-12-13

Relevant projects carried out within the Yangtze River economic belt on the impact of schistosomiasis epidemic and transmission are important issues for "ecological priority" in the process of implementing the strategy. The key problems of schistosomiasis epidemic risk, epidemic happening repeatedly, difficulty of rehabilitating Oncomelania hupensis snail control and schistosomiasis prevention forest, lag of evaluation system and platform construction, lack of basic research, et al. were analyzed in the Yangtze River economic belt taking "ecological priority" as the basis in this paper. Then corresponding countermeasures to these challenges were put forward so as to provide the reference for the national forestry schistosomiasis control programs, which include: execution of the comprehensive prevention and control strategy, scheming of the new round of forestry schistosomiasis control programs, strengthening schistosomiasis prevention and control, promoting productivity in existing forestry to consolidate and improve the achievements of previous forestry schistosomiasis control programs, and promoting the intensity of technological innovation to improve the technological level of forestry schistosomiasis control programs.

Space station thermal control surfaces. Volume 1: Interim report

NASA Technical Reports Server (NTRS)

Maag, C. R.; Millard, J. M.

1978-01-01

The U.S. space program goals for long-duration manned missions place particular demands on thermal-control systems. The objective of this program is to develop plans which are based on the present thermal-control technology, and which will keep pace with the other space program elements. The program tasks are as follows: (1) requirements analysis, with the objectives to define the thermal-control-surface requirements for both space station and 25 kW power module, to analyze the missions, and to determine the thermal-control-surface technology needed to satisfy both sets of requirements; (2) technology assessment, with the objectives to perform a literature/industry survey on thermal-control surfaces, to compare current technology with the requirements developed in the first task, and to determine what technology advancements are required for both the space station and the 25 kW power module; and (3) program planning that defines new initiative and/or program augmentation for development and testing areas required to provide the proper environment control for the space station and the 25 kW power module.

Controlled Aeroelastic Response and Airfoil Shaping Using Adaptive Materials and Integrated Systems

NASA Technical Reports Server (NTRS)

Pinkerton, Jennifer L.; McGowan, Anna-Maria R.; Moses, Robert W.; Scott, Robert C.; Heeg, Jennifer

1996-01-01

This paper presents an overview of several activities of the Aeroelasticity Branch at the NASA Langley Research Center in the area of applying adaptive materials and integrated systems for controlling both aircraft aeroelastic response and airfoil shape. The experimental results of four programs are discussed: the Piezoelectric Aeroelastic Response Tailoring Investigation (PARTI); the Adaptive Neural Control of Aeroelastic Response (ANCAR) program; the Actively Controlled Response of Buffet Affected Tails (ACROBAT) program; and the Airfoil THUNDER Testing to Ascertain Characteristics (ATTACH) project. The PARTI program demonstrated active flutter control and significant rcductions in aeroelastic response at dynamic pressures below flutter using piezoelectric actuators. The ANCAR program seeks to demonstrate the effectiveness of using neural networks to schedule flutter suppression control laws. Th,e ACROBAT program studied the effectiveness of a number of candidate actuators, including a rudder and piezoelectric actuators, to alleviate vertical tail buffeting. In the ATTACH project, the feasibility of using Thin-Layer Composite-Uimorph Piezoelectric Driver and Sensor (THUNDER) wafers to control airfoil aerodynamic characteristics was investigated. Plans for future applications are also discussed.

DARPA Internet Program. Internet and Transmission Control Specifications,

DTIC Science & Technology

1981-09-01

Internet Program Protocol Specification", RFC 791, USC/ Information Sciences Institute, September 1981. [34] Postel, J., ed., "Transmission Control Protocol...DARPA Internet Program Protocol Specification", RFC 793, USC/ Information Sciences Institute, September 1981. [35] Postel, J., "Echo Process", RFC 347...Newman, March 1981. [53] Postel, J., " Internet Control Message Protocol - DARPA Internet Program Protocol Specification", RFC 792, USC/ Information

Highly integrated digital electronic control: Digital flight control, aircraft model identification, and adaptive engine control

NASA Technical Reports Server (NTRS)

Baer-Riedhart, Jennifer L.; Landy, Robert J.

1987-01-01

The highly integrated digital electronic control (HIDEC) program at NASA Ames Research Center, Dryden Flight Research Facility is a multiphase flight research program to quantify the benefits of promising integrated control systems. McDonnell Aircraft Company is the prime contractor, with United Technologies Pratt and Whitney Aircraft, and Lear Siegler Incorporated as major subcontractors. The NASA F-15A testbed aircraft was modified by the HIDEC program by installing a digital electronic flight control system (DEFCS) and replacing the standard F100 (Arab 3) engines with F100 engine model derivative (EMD) engines equipped with digital electronic engine controls (DEEC), and integrating the DEEC's and DEFCS. The modified aircraft provides the capability for testing many integrated control modes involving the flight controls, engine controls, and inlet controls. This paper focuses on the first two phases of the HIDEC program, which are the digital flight control system/aircraft model identification (DEFCS/AMI) phase and the adaptive engine control system (ADECS) phase.

The value of partnerships in state obesity prevention and control programs.

PubMed

Hersey, James; Kelly, Bridget; Roussel, Amy; Curtis, LaShawn; Horne, Joseph; Williams-Piehota, Pamela; Kuester, Sarah; Farris, Rosanne

2012-03-01

State health departments funded by the Centers for Disease Control and Prevention's Nutrition, Physical Activity, and Obesity Program collaborate with multiple partners to develop and implement comprehensive obesity prevention and control programs. A mixed-methods evaluation of 28 state programs over a 5-year period assessed states' progress on program requirements, including developing statewide partnerships and coordinating with partners to support obesity prevention and control efforts. States with greater partnership involvement leveraged more funding support for their programs, passed more obesity-related policies, and were more likely to implement obesity interventions in multiple settings. Case studies provided guidance for establishing and maintaining strong partnerships. Findings from this study offer emerging evidence to support assumptions about the centrality of partnerships to states' success in obesity program development and implementation and related health promotion activities.

Aquatic Plant Control Research Program. Large-Scale Operations Management Test (LSOMT) of Insects and Pathogens for Control of Waterhyacinth in Louisiana. Volume 1. Results for 1979-1981.

DTIC Science & Technology

1985-01-01

RD-Ai56 759 AQUATIC PLANT CONTROL RESEARCH PROGRAM LARGE-SCALE 1/2 OPERATIONS MRNAGEMENT..(U) ARMY ENGINEER WATERAYS EXPERIMENT STATION VICKSBURG MS...PO Box 631, Vicksburg, Aquatic Plant Control Mississippi 39180-0631 and University of Research Program Tennessee-Chattanooga, Chattanooga, 12...19. KEY WORDS (Continue on reverse side if necesary nd identify by block number) - Aquatic plant control Louisiana Biological control Plant

Interactive Implementation of the Optimal Systems Control Design Program (OPTSYSX) on the IBM 3033.

DTIC Science & Technology

1984-03-01

DAS A44 159 INTERACTIVE IMPLEMENTATION OF THE OPTIMAL SYSTEMS I CONTROL DESIGN PROGRAM (OPTSYSX) ON THE 1DM 3033(U NAVAL POSTGRADUATE SCHOOL MONTEREY...noesear end idswtif’r b block number) Optimal Systems Control Systems Control Control Systems 10.; ABSTRACT (Continu an reveree side ff Roe684v ad Id yI...34 by block number) .- This thesis discusses the modification of an existing Optimal Systems Control FORTRAN program (OPTSYS) originally obtained from

Impact and cost-effectiveness of a comprehensive Schistosomiasis japonica control program in the Poyang Lake region of China.

PubMed

Yu, Qing; Zhao, Geng-Ming; Hong, Xian-Lin; Lutz, Eric A; Guo, Jia-Gang

2013-11-28

Schistosomiasis japonica remains a significant public-health problem in China. This study evaluated cost-effectiveness of a comprehensive schistosomiasis control program (2003-2006). The comprehensive control program was implemented in Zhangjia and Jianwu (cases); while standard interventions continued in Koutou and Xiajia (controls). Incurred costs were documented and the schistosomiasis comprehensive impact index (SCI) and cost-effectiveness ratio (Comprehensive Control Program Cost/SCI) were applied. In 2003, prevalence of Schistosoma japonicum infection was 11.3% (Zhangjia), 6.7% (Jianwu), 6.5% (Koutou), and 8.0% (Xiajia). In 2006, the comprehensive control program in Zhangjia and Jianwu reduced infection to 1.6% and 0.6%, respectively; while Koutou and Xiajia had a schistosomiasis prevalence of 3.2% and 13.0%, respectively. The year-by-year SCIs in Zhangjia were 0.28, 105.25, and 47.58, with an overall increase in cost-effectiveness ratio of 374.9%-544.8%. The SCIs in Jianwu were 16.21, 52.95, and 149.58, with increase in cost-effectiveness of 226.7%-1,149.4%. Investment in Koutou and Xiajia remained static (US$10,000 unit cost). The comprehensive control program implemented in the two case villages reduced median prevalence of schistosomiasis 8.5-fold. Further, the cost effectiveness ratio demonstrated that the comprehensive control program was 170% (Zhangjia) and 922.7% (Jianwu) more cost-effective. This work clearly shows the improvements in both cost and disease prevention effectiveness that a comprehensive control program-approach has on schistosomiasis infection prevalence.

Impact and Cost-Effectiveness of a Comprehensive Schistosomiasis japonica Control Program in the Poyang Lake Region of China

PubMed Central

Yu, Qing; Zhao, Geng-Ming; Hong, Xian-Lin; Lutz, Eric A.; Guo, Jia-Gang

2013-01-01

Schistosomiasis japonica remains a significant public-health problem in China. This study evaluated cost-effectiveness of a comprehensive schistosomiasis control program (2003–2006). The comprehensive control program was implemented in Zhangjia and Jianwu (cases); while standard interventions continued in Koutou and Xiajia (controls). Incurred costs were documented and the schistosomiasis comprehensive impact index (SCI) and cost-effectiveness ratio (Comprehensive Control Program Cost/SCI) were applied. In 2003, prevalence of Schistosoma japonicum infection was 11.3% (Zhangjia), 6.7% (Jianwu), 6.5% (Koutou), and 8.0% (Xiajia). In 2006, the comprehensive control program in Zhangjia and Jianwu reduced infection to 1.6% and 0.6%, respectively; while Koutou and Xiajia had a schistosomiasis prevalence of 3.2% and 13.0%, respectively. The year-by-year SCIs in Zhangjia were 0.28, 105.25, and 47.58, with an overall increase in cost-effectiveness ratio of 374.9%–544.8%. The SCIs in Jianwu were 16.21, 52.95, and 149.58, with increase in cost-effectiveness of 226.7%–1,149.4%. Investment in Koutou and Xiajia remained static (US$10,000 unit cost). The comprehensive control program implemented in the two case villages reduced median prevalence of schistosomiasis 8.5-fold. Further, the cost effectiveness ratio demonstrated that the comprehensive control program was 170% (Zhangjia) and 922.7% (Jianwu) more cost-effective. This work clearly shows the improvements in both cost and disease prevention effectiveness that a comprehensive control program-approach has on schistosomiasis infection prevalence. PMID:24287861

Performance seeking control program overview

NASA Technical Reports Server (NTRS)

Orme, John S.

1995-01-01

The Performance Seeking Control (PSC) program evolved from a series of integrated propulsion-flight control research programs flown at NASA Dryden Flight Research Center (DFRC) on an F-15. The first of these was the Digital Electronic Engine Control (DEEC) program and provided digital engine controls suitable for integration. The DEEC and digital electronic flight control system of the NASA F-15 were ideally suited for integrated controls research. The Advanced Engine Control System (ADECS) program proved that integrated engine and aircraft control could improve overall system performance. The objective of the PSC program was to advance the technology for a fully integrated propulsion flight control system. Whereas ADECS provided single variable control for an average engine, PSC controlled multiple propulsion system variables while adapting to the measured engine performance. PSC was developed as a model-based, adaptive control algorithm and included four optimization modes: minimum fuel flow at constant thrust, minimum turbine temperature at constant thrust, maximum thrust, and minimum thrust. Subsonic and supersonic flight testing were conducted at NASA Dryden covering the four PSC optimization modes and over the full throttle range. Flight testing of the PSC algorithm, conducted in a series of five flight test phases, has been concluded at NASA Dryden covering all four of the PSC optimization modes. Over a three year period and five flight test phases 72 research flights were conducted. The primary objective of flight testing was to exercise each PSC optimization mode and quantify the resulting performance improvements.

Investigation of air transportation technology at Princeton University, 1990-1991

NASA Technical Reports Server (NTRS)

Stengel, Robert F.

1991-01-01

The Air Transportation Technology Program at Princeton University is a program that emphasizes graduate and undergraduate student research. The program proceeded along six avenues during the past year: microburst hazards to aircraft, intelligent failure tolerant control, computer-aided heuristics for piloted flight, stochastic robustness of flight control systems, neural networks for flight control, and computer-aided control system design.

Self-Control Behavior of Drinking Drivers beyond the Context of a Behavioral Self-Control Program.

ERIC Educational Resources Information Center

Werch, Chudley E.

This paper reports on the post hoc analysis of specific types of self-control behaviors being employed by drinking drivers who were exposed to a behavioral self-control training program. The underlying assumption of this study is that the success of health promotion and intervention programs most probably depends on the development of greater…

News focus: Report on state and local air toxics regulatory strategies published by STAPPA/ALAPCO (State and Territorial Air Pollution Program Administrators/Association of Local Air Pollution Control Officials)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1989-12-01

The report is entitled Toxic Air Pollutants: State and Local Regulatory Strategies - 1989. The 364-page report is the result of a survey of state and local air pollution control agencies, which solicited information on their programs to control air toxics. According to the survey, every state currently has a program to address emissions of air toxics. Additionally, 27 of the 40 local agencies that responded to the survey have, or are developing, air toxics programs. The strategies employed by state and local agencies vary widely, including control technology requirements, risk assessment, acceptable ambient guidelines, or a combination of thesemore » approaches. This is a report summarizing the air toxics control programs currently implemented (or under development) by state and local air pollution control agencies throughout the US. The report is based upon a survey of all 50 states and 220 local air pollution control agencies conducted by the State and Territorial Air Pollution Program Administrators (STAPPA) and the Association of Local Air Pollution Control Officials (ALAPCO). This survey updates one published five years earlier.« less

78 FR 3390 - Agency Information Collection Activities: Proposed Collection; Comment Request-FNS-380, Worksheet...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... for the Supplemental Nutrition Assistance Program Quality Control Reviews AGENCY: Food and Nutrition... Nutrition Assistance Program's Quality Control Reviews. DATES: Written comments must be received on or...: Worksheet for the Supplemental Nutrition Assistance Program's (SNAP) Quality Control Reviews. Form Number...

Readings in program control

NASA Technical Reports Server (NTRS)

Hoban, Francis T. (Editor); Lawbaugh, William M. (Editor); Hoffman, Edward J. (Editor)

1994-01-01

Under the heading of Program Control, a number of related topics are discussed: cost estimating methods; planning and scheduling; cost overruns in the defense industry; the history of estimating; the advantages of cost plus award fee contracts; and how program control techniques led to the success of a NASA development project.

Computerized Numerical Control Curriculum Guide.

ERIC Educational Resources Information Center

Reneau, Fred; And Others

This guide is intended for use in a course in programming and operating a computerized numerical control system. Addressed in the course are various aspects of programming and planning, setting up, and operating machines with computerized numerical control, including selecting manual or computer-assigned programs and matching them with…

32 CFR 507.14 - Controlled heraldic items.

Code of Federal Regulations, 2010 CFR

2010-07-01

... HERALDIC DESIGNS AND HERALDIC QUALITY CONTROL PROGRAM Heraldic Quality Control Program § 507.14 Controlled..., U.S. Army. (d) U.S. Air Force organizational emblems for other than major commands. (e) Hand...

Strong tobacco control program requirements and secure funding are not enough: lessons from Florida.

PubMed

Kennedy, Allison; Sullivan, Sarah; Hendlin, Yogi; Barnes, Richard; Glantz, Stanton

2012-05-01

Florida's Tobacco Pilot Program (TPP; 1998-2003), with its edgy Truth media campaign, achieved unprecedented youth smoking reductions and became a model for tobacco control programming. In 2006, 3 years after the TPP was defunded, public health groups restored funding for tobacco control programming by convincing Florida voters to amend their constitution. Despite the new program's strong legal structure, Governor Charlie Crist's Department of Health implemented a low-impact program. Although they secured the program's strong structure and funding, Florida's nongovernmental public health organizations did not mobilize to demand a high-impact program. Implementation of Florida's Amendment 4 demonstrates that a strong programmatic structure and secure funding are insufficient to ensure a successful public health program, without external pressure from nongovernmental groups.

Publications of the NASA CELSS (Controlled Ecological Life Support Systems) program

NASA Technical Reports Server (NTRS)

Dufour, P. A.; Solberg, J. L.; Wallace, J. S.

1985-01-01

Publications on research sponsored by the NASA CELSS (controlled ecological life support systems) Program are listed. The bibliography is divided into four areas: (1) human requirements; (2) food production; (3) waste management; and (4) system management and control. The 210 references cover the period from the inception of the CELSS Program (1979) to the present, as well as some earlier publications during the development of the CELSS Program.

Organization of population-based cancer control programs: Europe and the world.

PubMed

Otter, Renée; Qiao, You-Lin; Burton, Robert; Samiei, Massoud; Parkin, Max; Trapido, Edward; Weller, David; Magrath, Ian; Sutcliffe, Simon

2009-01-01

As cancer is to a large extent avoidable and treatable, a cancer control program should be able to reduce mortality and morbidity and improve the quality of life of cancer patients and their families. However, the extent to which the goals of a cancer control program can be achieved will depend on the resource constraints a country faces. Such population-based cancer control plans should prioritize effective interventions and programs that are beneficial to the largest part of the population, and should include activities devoted to prevention, screening and early detection, treatment, palliation and end-of-life care, and rehabilitation. In order to develop a successful cancer control program, leadership and the relevant stakeholders, including patient organizations, need to be identified early on in the process so that all partners can take ownership and responsibility for the program. Various tools have been developed to aid them in the planning and implementation process. However, countries developing a national cancer control program would benefit from a discussion of different models for planning and delivery of population-based cancer control in settings with differing levels of resource commitment, in order to determine how best to proceed given their current level of commitment, political engagement and resources. As the priority assigned to different components of cancer control will differ depending on available resources and the burden and pattern of cancer, it is important to consider the relative roles of prevention, early detection, diagnosis, treatment, rehabilitation and palliative care in a cancer control program, as well as how to align available resources to meet prioritized needs. Experiences from countries with differing levels of resources are presented and serve to illustrate the difficulties in developing and implementing cancer control programs, as well as the innovative strategies that are being used to maximize available resources and enhance the quality of care provided to cancer patients around the world.

78 FR 77104 - Coastal Nonpoint Pollution Control Program: Intent To Find That Oregon Has Failed To Submit an...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration ENVIRONMENTAL PROTECTION AGENCY Coastal Nonpoint Pollution Control Program: Intent To Find That Oregon Has Failed To Submit an Approvable Coastal Nonpoint Pollution Control Program AGENCY: National Oceanic and Atmospheric Administration...

Programming Programmable Logic Controller. High-Technology Training Module.

ERIC Educational Resources Information Center

Lipsky, Kevin

This training module on programming programmable logic controllers (PLC) is part of the memory structure and programming unit used in a packaging systems equipment control course. In the course, students assemble, install, maintain, and repair industrial machinery used in industry. The module contains description, objectives, content outline,…

Making Youth Tobacco Control Programs More Ecological: Organizational and Professional Profiles.

ERIC Educational Resources Information Center

Richard, Lucie; Gauvin, Lise; Potvin, Louise; Denis, Jean-Louis; Kishchuk, Natalie

2002-01-01

Examined organizational and professional correlates of the integration of the ecological approach in Canadian public health organizations' youth tobacco control programs. Surveys of 110 tobacco control programs in 90 organizations indicated that organizational environment and staff preparation played a critical role in adoption of the ecological…

Rotorcraft flight-propulsion control integration

NASA Technical Reports Server (NTRS)

Mihaloew, James R.; Ballin, Mark G.; Ruttledge, D. G. C.

1988-01-01

The NASA Ames and Lewis Research Centers, in conjunction with the Army Research and Technology Laboratories have initiated and completed, in part, a joint research program focused on improving the performance, maneuverability, and operating characteristics of rotorcraft by integrating the flight and propulsion controls. The background of the program, its supporting programs, its goals and objectives, and an approach to accomplish them are discussed. Results of the modern control governor design of the T700 and the Rotorcraft Integrated Flight-Propulsion Control Study, which were key elements of the program, are also presented.

Analysis of tank 4 (FTF-4-15-22, 23) surface and subsurface supernatant samples in support of enrichment control, corrosion control and evaporator feed qualification programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oji, L. N.

This report provides the results of analyses on Savannah River Site Tank 4 surface and subsurface supernatant liquid samples in support of the Enrichment Control Program (ECP), the Corrosion Control Program (CCP) and the Evaporator Feed Qualification (EFQ) Program. The purpose of the ECP sample taken from Tank 4 in August 2015 was to determine if the supernatant liquid would be “acceptable feed” to the 2H and 3H evaporator systems.

Apollo experience report: Guidance and control systems. Mission control programmer for unmanned missions AS-202, Apollo 4, and Apollo 6

NASA Technical Reports Server (NTRS)

Holloway, G. F.

1975-01-01

An unmanned test flight program required to evaluate the command module heat shield and the structural integrity of the command and service module/Saturn launch vehicle is described. The mission control programer was developed to provide the unmanned interface between the guidance and navigation computer and the other spacecraft systems for mission event sequencing and real-time ground control during missions AS-202, Apollo 4, and Apollo 6. The development of this unmanned programer is traced from the initial concept through the flight test phase. Detailed discussions of hardware development problems are given with the resulting solutions. The mission control programer functioned correctly without any flight anomalies for all missions. The Apollo 4 mission control programer was reused for the Apollo 6 flight, thus being one of the first subsystems to be reflown on an Apollo space flight.

Application of digital computer APU modeling techniques to control system design.

NASA Technical Reports Server (NTRS)

Bailey, D. A.; Burriss, W. L.

1973-01-01

Study of the required controls for a H2-O2 auxiliary power unit (APU) technology program for the Space Shuttle. A steady-state system digital computer program was prepared and used to optimize initial system design. Analytical models of each system component were included. The program was used to solve a nineteen-dimensional problem, and then time-dependent differential equations were added to the computer program to simulate transient APU system and control. Some system parameters were considered quasi-steady-state, and others were treated as differential variables. The dynamic control analysis proceeded from initial ideal control modeling (which considered one control function and assumed the others to be ideal), stepwise through the system (adding control functions), until all of the control functions and their interactions were considered. In this way, the adequacy of the final control design over the required wide range of APU operating conditions was established.

Artificial intelligence programming with LabVIEW: genetic algorithms for instrumentation control and optimization.

PubMed

Moore, J H

1995-06-01

A genetic algorithm for instrumentation control and optimization was developed using the LabVIEW graphical programming environment. The usefulness of this methodology for the optimization of a closed loop control instrument is demonstrated with minimal complexity and the programming is presented in detail to facilitate its adaptation to other LabVIEW applications. Closed loop control instruments have variety of applications in the biomedical sciences including the regulation of physiological processes such as blood pressure. The program presented here should provide a useful starting point for those wishing to incorporate genetic algorithm approaches to LabVIEW mediated optimization of closed loop control instruments.

77 FR 19306 - Announcement of Funding Awards: Office of Healthy Homes and Lead Hazard Control Grant Programs...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... Federal Register notice published on May 18, 2011 for Lead Based Paint Hazard Control and Lead Hazard... Based Paint Hazard Control Grant Program A total of $43,206,000 was awarded to 22 grantees for the Lead Based Paint Hazard Control Grant Program and an additional $1,999,971 was awarded to 20 out of the 29...

77 FR 19305 - Announcement of Funding Awards: Office of Healthy Homes and Lead Hazard Control Grant Programs...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

... Federal Register notice published on September 9, 2010 for Lead Based Paint Hazard Control and Lead Hazard... follows: 1. Lead Based Paint Hazard Control Grant Program A total of $69,700,000 was awarded to 29 grantees for the Lead Based Paint Hazard Control Grant Program and an additional $2,388,637 was awarded to...

The NASA controls-structures interaction technology program

NASA Technical Reports Server (NTRS)

Newsom, Jerry R.; Layman, W. E.; Waites, H. B.; Hayduk, R. J.

1990-01-01

The interaction between a flexible spacecraft structure and its control system is commonly referred to as controls-structures interaction (CSI). The CSI technology program is developing the capability and confidence to integrate the structure and control system, so as to avoid interactions that cause problems and to exploit interactions to increase spacecraft capability. A NASA program has been initiated to advance CSI technology to a point where it can be used in spacecraft design for future missions. The CSI technology program is a multicenter program utilizing the resources of the NASA Langley Research Center (LaRC), the NASA Marshall Space Flight Center (MSFC), and the NASA Jet Propulsion Laboratory (JPL). The purpose is to describe the current activities, results to date, and future activities of the NASA CSI technology program.

A computer program for analyzing the energy consumption of automatically controlled lighting systems

NASA Astrophysics Data System (ADS)

1982-01-01

A computer code to predict the performance of controlled lighting systems with respect to their energy saving capabilities is presented. The computer program provides a mathematical model from which comparisons of control schemes can be made on an economic basis only. The program does not calculate daylighting, but uses daylighting values as input. The program can analyze any of three power input versus light output relationships, continuous dimming with a linear response, continuous dimming with a nonlinear response, or discrete stepped response. Any of these options can be used with or without daylighting, making six distinct modes of control system operation. These relationships are described in detail. The major components of the program are discussed and examples are included to explain how to run the program.

Toy Control Program evaluation.

PubMed

Stewart, H A; Ormond, C; Seeger, B R

1991-08-01

The Toy Control Program for the Apple IIe microcomputer is a software and hardware package developed for the training of single-switch scanning skills. The specially designed scanning programs provide on screen visual feedback and activate a battery-powered toy to reinforce performance. This study examined whether the training of preschool subjects in single-switch scanning skills with the Toy Control Program would result in increased task completion scores and increased levels of attention to task, as compared with conditions of toy activation only and microcomputer programs with screen reinforcement only. The results showed that the subjects paid significantly more attention to the toys as reinforcers (p less than .01). No significant difference was found for the performance results of the three conditions. These findings support the use of a program like the Toy Control Program, which integrates the instructional capabilities of a computer with the reinforcement potential of a toy and the creativity of a therapist.

Medicaid/CHIP Program; Medicaid Program and Children's Health Insurance Program (CHIP); Changes to the Medicaid Eligibility Quality Control and Payment Error Rate Measurement Programs in Response to the Affordable Care Act. Final rule.

PubMed

2017-07-05

This final rule updates the Medicaid Eligibility Quality Control (MEQC) and Payment Error Rate Measurement (PERM) programs based on the changes to Medicaid and the Children's Health Insurance Program (CHIP) eligibility under the Patient Protection and Affordable Care Act. This rule also implements various other improvements to the PERM program.

Opportunity for collaboration: a conceptual model of success in tobacco control and cancer prevention.

PubMed

Stillman, Frances A; Schmitt, Carol L; Rosas, Scott R

2012-01-01

Collaborations between cancer prevention and tobacco control programs can leverage scarce resources to address noncommunicable diseases globally, but barriers to cooperation and actual collaboration are substantial. To foster collaboration between cancer prevention and tobacco control programs, the Global Health Partnership conducted research to identify similarities and differences in how the 2 programs viewed program success. Using concept mapping, cancer prevention and tobacco control experts generated statements describing the components of a successful cancer prevention or tobacco control program and 33 participants sorted and rated the final 99 statements. Multidimensional scaling analysis with a 2-dimensional solution was used to identify an 8-cluster conceptual map of program success. We calculated Pearson correlation coefficients for all 99 statements to compare the item-level ratings of both groups and used t tests to compare the mean importance of ratings assigned to each cluster. Eight major clusters of success were identified: 1) advocacy and persuasion, 2) building sustainability, 3) partnerships, 4) readiness and support, 5) program management fundamentals, 6) monitoring and evaluation, 7) utilization of evidence, and 8) implementation. We found no significant difference between the maps created by the 2 groups and only 1 mean difference for the importance ratings for 1 of the clusters: cancer prevention experts rated partnerships as more important to program success than did tobacco control experts. Our findings are consistent with those of research documenting the necessary components of successful programs and the similarities between cancer prevention and tobacco control. Both programs value the same strategies to address a common risk factor: tobacco use. Identifying common ground between these 2 research and practice communities can benefit future collaborations at the local, state, tribal, national, and international levels, and inform the broader discussion on resource sharing among other organizations whose mission focuses on noncommunicable diseases.

40 CFR 147.50 - State-administered program-Class II wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Carry Out Underground Injection Control Program Relating to Class II Wells as Described in Federal Safe... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alabama... application: (a) Incorporation by reference. The requirements set forth in the State statutes and regulations...

Comprehensive Erosion and Sediment Control Training Program for Job Superintendents and Inspectors.

ERIC Educational Resources Information Center

Porter, Harry L., Jr.

One of two training program texts built around the Virginia Erosion and Sediment Control Law and Program, this guide presents a program designed to meet the needs of job superintendents and inspectors. (The other guide, containing a program for engineers, architects, and planners, was designed to train professional people who need engineering and…

Effects of a 10-week weight control program on obese patients with schizophrenia or schizoaffective disorder: a 12-month follow up.

PubMed

Chen, Chih-Ken; Chen, Yi-Chih; Huang, Yu-Shu

2009-02-01

Weight gain secondary to antipsychotic medication is associated with many serious conditions, including type II diabetes mellitus, hypertension, and coronary heart disease, and also with poor medication compliance. Weight control programs may be of benefit to outpatients with schizophrenia, but also raise an issue of cost-effectiveness. We aimed to evaluate the effectiveness of a 10-week weight control program for outpatients taking atypical antipsychotics for treatment of schizophrenia, and to follow up the effects of this weight control program in controlling weight gain after termination of the program. A total of 33 patients with schizophrenia and antipsychotic-related obesity were enrolled in a 10-week multimodal weight control program. The patients' weights were recorded at baseline, week 4, week 8, week 10 (end of the intervention), week 12, week 24, and week 48. Secondary measures included blood sugar levels, cholesterol levels, triglyceride levels, quality of life and mental health. For those who completed the weight control program, there was a mean weight loss of 2.1 kg by the end of the intervention, 3.7 kg over 6 months, and 2.7 kg over 12 months. The mean body mass index decreased by 0.8, 1.5 and 1.1 at week 10, week 24 and week 48, respectively, all with statistical significance. The 10-week weight control program was effective in terms of weight reduction among obese patients with schizophrenia or schizoaffective disorder, and the weight reduction effect lasted for up to 6 months, and up to 12 months in some cases.

Indicators of asthma control among students in a rural, school-based asthma management program

PubMed Central

Rasberry, Catherine N.; Cheung, Karen; Buckley, Rebekah; Dunville, Richard; Daniels, Brandy; Cook, Deborah; Robin, Leah; Dean, Blair

2015-01-01

Objective The evaluation sought to determine if a comprehensive, school-based asthma management program in a small, rural school district helped students improve asthma control. Methods To determine if students in the asthma program demonstrated better asthma control than students in a comparison school district, the evaluation team used a quasi-experimental, cross-sectional design and administered questionnaires assessing asthma control (which included FEV1 measurement) to 456 students with asthma in the intervention and comparison districts. Data were analyzed for differences in asthma control between students in the two districts. To determine if students in the intervention experienced increased asthma control between baseline and follow-up, the evaluation team used a one-group retrospective design. Program records for 323 students were analyzed for differences in percent of predicted forced expiratory volume in one second (FEV1) between baseline and follow-up. Results Students with asthma in the intervention district exhibited significantly better asthma control than students with asthma in the comparison district. Percent of predicted FEV1 did not change significantly between baseline and follow-up for the intervention participants; however, post hoc analyses revealed students with poorly-controlled asthma at baseline had significantly higher FEV1 scores at follow-up, and students with well-controlled asthma at baseline had significantly lower FEV1 scores at follow-up. Conclusions Findings suggest the comprehensive school-based program led to improvements in asthma control for students with poorly controlled asthma at baseline, and school-based programs need mechanisms for tracking students with initially well-controlled asthma in order to ensure they maintain control. PMID:24730771

Self-teaching digital-computer program for fail-operational control of a turbojet engine in a sea-level test stand

NASA Technical Reports Server (NTRS)

Wallhagen, R. E.; Arpasi, D. J.

1974-01-01

The design and evaluation are described of a digital turbojet engine control which is capable of sensing catastrophic failures in either the engine rotor speed or the compressor discharge static-pressure signal and is capable of switching control modes to maintain near normal operation. The control program was developed for and tested on a turbojet engine located in a sea-level test stand. The control program is also capable of acquiring all the data that are necessary for the fail-operational control to function.

Integrated Digital Flight Control System for the Space Shuttle Orbiter

NASA Technical Reports Server (NTRS)

1973-01-01

The objectives of the integrated digital flight control system (DFCS) is to provide rotational and translational control of the space shuttle orbiter in all phases of flight: from launch ascent through orbit to entry and touchdown, and during powered horizontal flights. The program provides a versatile control system structure while maintaining uniform communications with other programs, sensors, and control effectors by using an executive routine/functional subroutine format. The program reads all external variables at a single point, copies them into its dedicated storage, and then calls the required subroutines in the proper sequence. As a result, the flight control program is largely independent of other programs in the computer complex and is equally insensitive to characteristics of the processor configuration. The integrated structure is described of the control system and the DFCS executive routine which embodies that structure. The input and output, including jet selection are included. Specific estimation and control algorithm are shown for the various mission phases: cruise (including horizontal powered flight), entry, on-orbit, and boost. Attitude maneuver routines that interface with the DFCS are included.

Dissonance and Healthy Weight Eating Disorder Prevention Programs: Long-Term Effects from a Randomized Efficacy Trial

ERIC Educational Resources Information Center

Stice, Eric; Marti, C. Nathan; Spoor, Sonja; Presnell, Katherine; Shaw, Heather

2008-01-01

Adolescent girls with body dissatisfaction (N = 481, SD = 1.4) were randomized to a dissonance-based thin-ideal internalization reduction program, healthy weight control program, expressive writing control condition, or assessment-only control condition. Dissonance participants showed significantly greater decreases in thin-ideal internalization,…

42 CFR 431.810 - Basic elements of the Medicaid eligibility quality control (MEQC) program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Basic elements of the Medicaid eligibility quality control (MEQC) program. 431.810 Section 431.810 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... elements of the Medicaid eligibility quality control (MEQC) program. (a) General requirements. The agency...

75 FR 8239 - School Food Safety Program Based on Hazard Analysis and Critical Control Point Principles (HACCP...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

... 0584-AD65 School Food Safety Program Based on Hazard Analysis and Critical Control Point Principles... Safety Program Based on Hazard Analysis and Critical Control Point Principles (HACCP) was published on... of Management and Budget (OMB) cleared the associated information collection requirements (ICR) on...

Our Cost Control Program Is Real, and Good PR Too.

ERIC Educational Resources Information Center

Harris, James; And Others

The cost control program of the Beaverton School District (Oregon) is presented in three sections. Reviewing the role of the school board in cost control development, Jean Holt (a board member) outlines the fiscal management system, long-range financial strategies, energy conservation, and utilization of facilities. The programs have resulted in a…

Propulsion system/flight control integration for supersonic aircraft

NASA Technical Reports Server (NTRS)

Reukauf, P. J.; Burcham, F. W., Jr.

1976-01-01

Digital integrated control systems are studied. Such systems allow minimization of undesirable interactions while maximizing performance at all flight conditions. One such program is the YF-12 cooperative control program. The existing analog air data computer, autothrottle, autopilot, and inlet control systems are converted to digital systems by using a general purpose airborne computer and interface unit. Existing control laws are programed and tested in flight. Integrated control laws, derived using accurate mathematical models of the airplane and propulsion system in conjunction with modern control techniques, are tested in flight. Analysis indicates that an integrated autothrottle autopilot gives good flight path control and that observers are used to replace failed sensors.

Enhancing the educational achievement of at-risk youth.

PubMed

Schinke, S P; Cole, K C; Poulin, S R

2000-03-01

This study examined a non-school program aimed at enhancing the educational performance of economically disadvantaged early adolescents who live in public housing. The educational enhancement program included discussions with adults, writing activities, leisure reading, homework, helping others, and games using cognitive skills. A three-arm research design juxtaposed program youth who received educational enhancements with comparison youth in affiliated facilities who did not receive the program and with control youth in other community programs without educational enhancements. From youths, follow-up data collected 2 1/2 years after baseline revealed uniformly positive outcomes for program youth on measures of reading, verbal skills, writing, and tutoring. Teacher reports at final follow-up favored program and comparison youth over controls on measures of reading, writing, games, overall school performance, and interest in class material. School grades were higher for program youth than for comparison and control youth for reading, spelling, history, science, and social studies. Overall grade averages were higher for program youth versus comparisons and controls, as was school attendance. Study data lend empirical support to the provision of educational enhancements in non-school settings for at-risk youths.

Schemes for Oestrus Synchronization Protocols and Controlled Breeding Programs in Cattle

NASA Astrophysics Data System (ADS)

Sabo, Y. G.; Sandabe, U. K.; Maina, V. A.; Balla, H. G.

Today prostaglandin and progesterone has been found widely used in several schemes of oestrus synchronization and controlled breeding program. Several controlled breeding program, have been developed for synchronizing groups of all open or lactating cows within a breeding group with or without ovarian palpation. Such programs are reviewed in this article which involves extending the luteal phase by treatment with exogenous progesterone such as: progesterone treatment regimes using syncro-mate-B, progesterone releasing intravaginal device, melengesterol acetate-select and melegestrol acetate plus prostaglandin. Also reviewed in the program is the termination of the luteal phase by treatment with prostaglandin or its analogues. These includes, controlled breeding without ovarian palpation such as, the 7-days program; 11-days program, target breeding, ovsynch program, Heat synch, Cosynch and pre synch-ovsynch program. In our opinion full potential of progesterone and prostaglandin for the detection of oestrus and timed artificial insemination should be utilized. This reduces the much labour input employed in previous years. The practitioner of the livestock herd health must-develop strategies for the delivery of this technology to livestock farmers, its use and limitations.

Apollo guidance, navigation and control: Guidance system operations plan for manned CM earth orbital and lunar missions using Program COLOSSUS 3. Section 3: Digital autopilots (revision 14)

NASA Technical Reports Server (NTRS)

1972-01-01

Digital autopilots for the manned command module earth orbital and lunar missions using program COLOSSUS 3 are discussed. Subjects presented are: (1) reaction control system digital autopilot, (2) thrust vector control autopilot, (3) entry autopilot and mission control programs, (4) takeover of Saturn steering, and (5) coasting flight attitude maneuver routine.

Structure and management of tuberculosis control programs in fragile states--Afghanistan, DR Congo, Haiti, Somalia.

PubMed

Mauch, Verena; Weil, Diana; Munim, Aayid; Boillot, Francois; Coninx, Rudi; Huseynova, Sevil; Powell, Clydette; Seita, Akihiro; Wembanyama, Henriette; van den Hof, Susan

2010-07-01

Health care delivery is particularly problematic in fragile states often connected with increased incidence of communicable diseases, among them tuberculosis. This article draws upon experiences in tuberculosis control in four fragile states from which four lessons learned were derived. A structured inventory to extract common themes specific for TB control in fragile states was conducted among twelve providers of technical assistance who have worked in fragile states. The themes were applied to the TB control programs of Afghanistan, DR Congo, Haiti and Somalia during the years 2000-2006. Case notifications and treatment outcomes have increased in all four countries since 2003 (treatment success rates 81-90%). Access to care and case detection however have remained insufficient (case detection rates 39-62%); There are four lessons learned: 1. TB control programs can function in fragile states. 2. National program leadership and stewardship are essential for quality and sustained TB control. 3. Partnerships with non-governmental providers are vital for continuous service delivery; 4. TB control programs in fragile states require consistent donor support. Despite challenges in management, coordination, security, logistics and funding, TB control programs can function in fragile states, but face considerable problems in access to diagnosis and treatment and therefore case detection. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Can your software engineer program your PLC?

NASA Astrophysics Data System (ADS)

Borrowman, Alastair J.; Taylor, Philip

2016-07-01

The use of Programmable Logic Controllers (PLCs) in the control of large physics experiments is ubiquitous1, 2, 3. The programming of these controllers is normally the domain of engineers with a background in electronics, this paper introduces PLC program development from the software engineer's perspective. PLC programs provide the link between control software running on PC architecture systems and physical hardware controlled and monitored by digital and analog signals. The higher-level software running on the PC is typically responsible for accepting operator input and from this deciding when and how hardware connected to the PLC is controlled. The PLC accepts demands from the PC, considers the current state of its connected hardware and if correct to do so (based upon interlocks or other constraints) adjusts its hardware output signals appropriately for the PC's demands. A published ICD (Interface Control Document) defines the PLC memory locations available to be written and read by the PC to control and monitor the hardware. Historically the method of programming PLCs has been ladder diagrams that closely resemble circuit diagrams, however, PLC manufacturers nowadays also provide, and promote, the use of higher-level programming languages4. Based on techniques used in the development of high-level PC software to control PLCs for multiple telescopes, this paper examines the development of PLC programs to operate the hardware of a medical cyclotron beamline controlled from a PC using the Experimental Physics and Industrial Control System (EPICS), which is also widely used in telescope control5, 6, 7. The PLC used is the new generation Siemens S7-1200 programmed using Siemens Pascal based Structured Control Language (SCL), which is their implementation of Structured Text (ST). The approach described is that from a software engineer's perspective, utilising Siemens Totally Integrated Automation (TIA) Portal integrated development environment (IDE) to create modular PLC programs based upon reusable functions capable of being unit tested without the PLC connected to hardware. Emphasis has been placed on designing an interface between EPICS and SCL that enforces correct operation of hardware through stringent separation of PC accessible PLC memory and hardware I/O addresses used only by the PLC. The paper also introduces the method used to automate the creation, from the same source document, the PLC memory structure (tag) definitions (defining memory used to access hardware I/O and that accessed by the PC) and creation of the PC program data structures (EPICS database records) used to access the permitted PLC addresses. From direct experience this paper demonstrates the advantages of PLC program development being shared between electronic and software engineers, to enable use of the most appropriate processes from both the perspective of the hardware and the higher-level software used to control it.

40 CFR 141.71 - Criteria for avoiding filtration.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.71... water. (2) The public water system must maintain a watershed control program which minimizes the... determine whether the watershed control program is adequate to meet this goal. The adequacy of a program to...

Master control data handling program uses automatic data input

NASA Technical Reports Server (NTRS)

Alliston, W.; Daniel, J.

1967-01-01

General purpose digital computer program is applicable for use with analysis programs that require basic data and calculated parameters as input. It is designed to automate input data preparation for flight control computer programs, but it is general enough to permit application in other areas.

7 CFR 785.13 - OMB Control Number.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 7 2012-01-01 2012-01-01 false OMB Control Number. 785.13 Section 785.13 Agriculture... SPECIAL PROGRAMS CERTIFIED STATE MEDIATION PROGRAM § 785.13 OMB Control Number. The information collection... control number 0560-0165. ...

Quality controls for gamma cameras and PET cameras: development of a free open-source ImageJ program

NASA Astrophysics Data System (ADS)

Carlier, Thomas; Ferrer, Ludovic; Berruchon, Jean B.; Cuissard, Regis; Martineau, Adeline; Loonis, Pierre; Couturier, Olivier

2005-04-01

Acquisition data and treatments for quality controls of gamma cameras and Positron Emission Tomography (PET) cameras are commonly performed with dedicated program packages, which are running only on manufactured computers and differ from each other, depending on camera company and program versions. The aim of this work was to develop a free open-source program (written in JAVA language) to analyze data for quality control of gamma cameras and PET cameras. The program is based on the free application software ImageJ and can be easily loaded on any computer operating system (OS) and thus on any type of computer in every nuclear medicine department. Based on standard parameters of quality control, this program includes 1) for gamma camera: a rotation center control (extracted from the American Association of Physics in Medicine, AAPM, norms) and two uniformity controls (extracted from the Institute of Physics and Engineering in Medicine, IPEM, and National Electronic Manufacturers Association, NEMA, norms). 2) For PET systems, three quality controls recently defined by the French Medical Physicist Society (SFPM), i.e. spatial resolution and uniformity in a reconstructed slice and scatter fraction, are included. The determination of spatial resolution (thanks to the Point Spread Function, PSF, acquisition) allows to compute the Modulation Transfer Function (MTF) in both modalities of cameras. All the control functions are included in a tool box which is a free ImageJ plugin and could be soon downloaded from Internet. Besides, this program offers the possibility to save on HTML format the uniformity quality control results and a warning can be set to automatically inform users in case of abnormal results. The architecture of the program allows users to easily add any other specific quality control program. Finally, this toolkit is an easy and robust tool to perform quality control on gamma cameras and PET cameras based on standard computation parameters, is free, run on any type of computer and will soon be downloadable from the net (http://rsb.info.nih.gov/ij/plugins or http://nucleartoolkit.free.fr).

Cox report and the US-China arms control technical exchange program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Capua, M S

The ACE program furthered the national security interests of the US by promoting technical approaches to the implementation and verification of arms control treaties that the international community embraces. The Cox Committee report suggests that uncontrolled interactions were taking place between US and Chinese nuclear weapons scientists in the course of the ACE program. On the contrary, elaborate controls were in place at the very beginning and remained in place to control the interactions and protect US national security information. The ACE program payoff to national security was just beginning and its suspension, resulting from the Cox reports allegations, ismore » a setback to US-China progress on arms control.« less

INFECTION CONTROL IN ALTERNATIVE HEALTHCARE SETTINGS

PubMed Central

Flanagan, Elaine; Chopra, Teena; Mody, Lona

2011-01-01

SYNOPSIS With the changing healthcare delivery, patients receive care at various settings including acute care hospitals, skilled nursing facilities, outpatient primary care and specialty clinics, as well as at home, exposing them to pathogens in various settings. Various healthcare settings face unique challenges requiring individualized infection control programs. Infection control programs in skilled nursing facilities should address: surveillance for infections and antimicrobial resistance, outbreak investigation and control plan for epidemics, isolation precautions, hand hygiene, staff education, and employee and resident health programs. Infection control programs in ambulatory clinics should address: Triage and standard – transmission based precautions, cleaning, disinfection and sterilization principles, surveillance in surgical clinics, safe injection practices, and bioterrorism and disaster planning for ambulatory clinics. PMID:21316005

Sensitivity Analysis of Linear Programming and Quadratic Programming Algorithms for Control Allocation

NASA Technical Reports Server (NTRS)

Frost, Susan A.; Bodson, Marc; Acosta, Diana M.

2009-01-01

The Next Generation (NextGen) transport aircraft configurations being investigated as part of the NASA Aeronautics Subsonic Fixed Wing Project have more control surfaces, or control effectors, than existing transport aircraft configurations. Conventional flight control is achieved through two symmetric elevators, two antisymmetric ailerons, and a rudder. The five effectors, reduced to three command variables, produce moments along the three main axes of the aircraft and enable the pilot to control the attitude and flight path of the aircraft. The NextGen aircraft will have additional redundant control effectors to control the three moments, creating a situation where the aircraft is over-actuated and where a simple relationship does not exist anymore between the required effector deflections and the desired moments. NextGen flight controllers will incorporate control allocation algorithms to determine the optimal effector commands and attain the desired moments, taking into account the effector limits. Approaches to solving the problem using linear programming and quadratic programming algorithms have been proposed and tested. It is of great interest to understand their relative advantages and disadvantages and how design parameters may affect their properties. In this paper, we investigate the sensitivity of the effector commands with respect to the desired moments and show on some examples that the solutions provided using the l2 norm of quadratic programming are less sensitive than those using the l1 norm of linear programming.

STOVL aircraft simulation for integrated flight and propulsion control research

NASA Technical Reports Server (NTRS)

Mihaloew, James R.; Drummond, Colin K.

1989-01-01

The United States is in the initial stages of committing to a national program to develop a supersonic short takeoff and vertical landing (STOVL) aircraft. The goal of the propulsion community in this effort is to have the enabling propulsion technologies for this type aircraft in place to permit a low risk decision regarding the initiation of a research STOVL supersonic attack/fighter aircraft in the late mid-90's. This technology will effectively integrate, enhance, and extend the supersonic cruise, STOVL and fighter/attack programs to enable U.S. industry to develop a revolutionary supersonic short takeoff and vertical landing fighter/attack aircraft in the post-ATF period. A joint NASA Lewis and NASA Ames research program, with the objective of developing and validating technology for integrated-flight propulsion control design methodologies for short takeoff and vertical landing (STOVL) aircraft, was planned and is underway. This program, the NASA Supersonic STOVL Integrated Flight-Propulsion Controls Program, is a major element of the overall NASA-Lewis Supersonic STOVL Propulsion Technology Program. It uses an integrated approach to develop an integrated program to achieve integrated flight-propulsion control technology. Essential elements of the integrated controls research program are realtime simulations of the integrated aircraft and propulsion systems which will be used in integrated control concept development and evaluations. This paper describes pertinent parts of the research program leading up to the related realtime simulation development and remarks on the simulation structure to accommodate propulsion system hardware drop-in for real system evaluation.

Rotorcraft flight-propulsion control integration: An eclectic design concept

NASA Technical Reports Server (NTRS)

Mihaloew, James R.; Ballin, Mark G.; Ruttledge, D. C. G.

1988-01-01

The NASA Ames and Lewis Research Centers, in conjunction with the Army Research and Technology Laboratories, have initiated and partially completed a joint research program focused on improving the performance, maneuverability, and operating characteristics of rotorcraft by integrating the flight and propulsion controls. The background of the program, its supporting programs, its goals and objectives, and an approach to accomplish them are discussed. Results of the modern control governor design of the General Electric T700 engine and the Rotorcraft Integrated Flight-Propulsion Control Study, which were key elements of the program, are also presented.

Man-rated flight software for the F-8 DFBW program

NASA Technical Reports Server (NTRS)

Bairnsfather, R. R.

1976-01-01

The design, implementation, and verification of the flight control software used in the F-8 DFBW program are discussed. Since the DFBW utilizes an Apollo computer and hardware, the procedures, controls, and basic management techniques employed are based on those developed for the Apollo software system. Program assembly control, simulator configuration control, erasable-memory load generation, change procedures and anomaly reporting are discussed. The primary verification tools are described, as well as the program test plans and their implementation on the various simulators. Failure effects analysis and the creation of special failure generating software for testing purposes are described.

Making real-time reactive systems reliable

NASA Technical Reports Server (NTRS)

Marzullo, Keith; Wood, Mark

1990-01-01

A reactive system is characterized by a control program that interacts with an environment (or controlled program). The control program monitors the environment and reacts to significant events by sending commands to the environment. This structure is quite general. Not only are most embedded real time systems reactive systems, but so are monitoring and debugging systems and distributed application management systems. Since reactive systems are usually long running and may control physical equipment, fault tolerance is vital. The research tries to understand the principal issues of fault tolerance in real time reactive systems and to build tools that allow a programmer to design reliable, real time reactive systems. In order to make real time reactive systems reliable, several issues must be addressed: (1) How can a control program be built to tolerate failures of sensors and actuators. To achieve this, a methodology was developed for transforming a control program that references physical value into one that tolerates sensors that can fail and can return inaccurate values; (2) How can the real time reactive system be built to tolerate failures of the control program. Towards this goal, whether the techniques presented can be extended to real time reactive systems is investigated; and (3) How can the environment be specified in a way that is useful for writing a control program. Towards this goal, whether a system with real time constraints can be expressed as an equivalent system without such constraints is also investigated.

A Health Belief Model-Social Learning Theory approach to adolescents' fertility control: findings from a controlled field trial.

PubMed

Eisen, M; Zellman, G L; McAlister, A L

1992-01-01

We evaluated an 8- to 12-hour Health Belief Model-Social Learning Theory (HBM-SLT)-based sex education program against several community- and school-based interventions in a controlled field experiment. Data on sexual and contraceptive behavior were collected from 1,444 adolescents unselected for gender, race/ethnicity, or virginity status in a pretest-posttest design. Over 60% completed the one-year follow-up. Multivariate analyses were conducted separately for each preintervention virginity status by gender grouping. The results revealed differential program impacts. First, for preintervention virgins, there were no gender or intervention differences in abstinence maintenance over the follow-up year. Second, female preintervention Comparison program virgins used effective contraceptive methods more consistently than those who attended the HBM-SLT program (p less than 0.01); among males, the intervention programs were equally effective. Third, both interventions significantly increased contraceptive efficiency for teenagers who were sexually active before attending the programs. For males, the HBM-SLT program led to significantly greater follow-up contraceptive efficiency than the Comparison program with preintervention contraceptive efficiency controlled (p less than 0.05); for females, the programs produced equivalent improvement. Implications for program planning and evaluation are discussed.

Developing an Information and Records Management Program.

ERIC Educational Resources Information Center

Rutledge, Juli G.; Kartis, Alexia M.

1984-01-01

The need for information controls for college records management programs and the elements of program organization, planning, and management are discussed. Conditions at institutions that indicate a flaw in information control are identified, along with the benefits of a sound records management program. The management of an information and…

44 CFR Appendix B to Part 62 - National Flood Insurance Program

Code of Federal Regulations, 2012 CFR

2012-10-01

... obtain a copy of “The Write Your Own Program Financial Control Plan Requirements and Procedures” by... Plan to Maintain Financial Control for Business Written Under the Write Your Own Program. (a) In general. Under the Write Your Own (WYO) Program, we (the Federal Insurance Administration (FIA), Federal...

Space shuttle environmental and thermal control life support system computer program

NASA Technical Reports Server (NTRS)

1972-01-01

A computer program for the design and operation of the space shuttle environmental and thermal control life support system is presented. The subjects discussed are: (1) basic optimization program, (2) off design performance, (3) radiator/evaporator expendable usage, (4) component weights, and (5) computer program operating procedures.

Self-Image Development: A Chicano Enfasis. Self-Programmed Counseling and Self-Programmed Control. Instructor's Guide = Desarrollo de la Imagen Propia: Enfasis en el Chicano. Sistema de Consejo y Control Auto-Programado. Manuel del Profesor.

ERIC Educational Resources Information Center

Mireles, S. Raymond

Self-Programmed Counseling, the instructor's guidance, and Self-Programmed Control (SPC), the student's response, was initially developed by Title III Project USTED (United Students and Teachers for Educational Development) for Mexican American students on academic probation to use on a non-credit, special group counseling basis. As part of a…

Checkout/demonstration application program for the SEL 840MP Multi-Processing Control System: Version 1 (MPCS/1)

NASA Technical Reports Server (NTRS)

Anderson, W. F.; Conway, J. R.; Keller, L. C.

1972-01-01

The characteristics of the application program were developed to verify and demonstrate the SEL 840MP Multi-Processing Control System - Version I (MPCS/1). The application program emphasizes the display support and task control capabilities. The application program is further intended to be used as an aid to familization with MPCS/1. It complements the information provided in the MPCS/1 Users Guide, Volume I and II.

Evaluation of a standardized patient education program for inpatient asthma rehabilitation: Impact on patient-reported health outcomes up to one year.

PubMed

Bäuerle, Kathrin; Feicke, Janine; Scherer, Wolfgang; Spörhase, Ulrike; Bitzer, Eva-Maria

2017-05-01

To modify and evaluate a patient education program for adult asthma patients in consideration of quality criteria for teaching. This was a prospective single-center controlled trial in an inpatient rehabilitation center. The control group (n=215) received the usual lecture-based education program, and the intervention group (n=209) the modified patient education program. Data were assessed at admission, discharge, 6 and 12 months post discharge. The primary outcome was asthma control, the secondary outcomes were asthma knowledge, quality of life, and program acceptance. Analysis of change was performed by ANCOVA for each follow-up, adjusting for baseline values. Statistically significant increases in all health outcomes and in asthma control were maintained in both groups at 12 months: CG: +1.9 (95%-CI 1.3-2.6) IG: +1.6 (95%-CI 0.8-2.3). We observed no significant differences between the programs for asthma control and quality of life. Regarding practical asthma knowledge, after 12 months, a group*time interaction emerged with a small effect size (P=0.06, η2=0.01). The modified program was not superior to traditional patient education concerning asthma control. It permanently increased self-management knowledge. Structured and behavioral patient education fosters patient's disease management ability. Possible ways of improving asthma control need to be explored. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A summary of joint US-Canadian augmentor wing powered-lift STOL research programs at the Ames Research Center, NASA, 1975-1980

NASA Technical Reports Server (NTRS)

Hindson, W. S.; Hardy, G.

1980-01-01

Several different flight research programs carried out by NASA and the Canadian Government using the Augmentor Wing Jet STOL Research Aircraft to investigate the design, operational, and systems requirements for powered-lift STOL aircraft are summarized. Some of these programs considered handling qualities and certification criteria for this class of aircraft, and addressed pilot control techniques, control system design, and improved cockpit displays for the powered-lift STOL approach configuration. Other programs involved exploiting the potential of STOL aircraft for constrained terminal-area approaches within the context of present or future air traffic control environments. Both manual and automatic flight control investigations are discussed, and an extensive bibliography of the flight programs is included.

Coercive versus cooperative pollution control: Comparative study of state programs to reduce erosion and sedimentation pollution in urban areas

NASA Astrophysics Data System (ADS)

Burby, Raymond J.

1995-05-01

This article examines coercive and cooperative approaches to implementing state urban erosion and sedimentation pollution control programs. State administrators report serious shortfalls in their ability to control sources of pollution, but comparison of more and less successful programs provides evidence of what states can do to make programs more effective. Key ingredients for a successful state effort include the use of coercion with both the private sector and local government, adequate staffing, application of severe sanctions when violations of state standards are detected, and provision of technical assistance. Many state programs lack one or more of those elements, which explains their inability to adequately control urban erosion and sedimentation pollution.

Meteorology program of the National Center for Air Pollution Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ludwig, J.H.; McCormick, R.A.

1968-08-01

An attempt is made to discuss the role of the meteorologist in the Federal air pollution programs. There are two types of meteorological activities that have evolved as a result of the Federal air pollution program to aid the states and local agencies in their efforts to control air pollution. They are: research, which has focused on defining and describing meteorological factors of prime importance to air pollution control activities; and application of meteorological principles to the conduct of air pollution control programs. A detailed discussion is presented of the meteorological activities of the National Center for Air Pollution Controlmore » and their close relationships to other phases of the Center's research and operational programs.« less

Measurement control workshop instructional materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gibbs, Philip; Harvel, Charles; Clark, John

2012-09-01

An essential element in an effective nuclear materials control and accountability (MC&A) program is the measurement of the nuclear material as it is received, moved, processed and shipped. Quality measurement systems and methodologies determine the accuracy of the accountability values. Implementation of a measurement control program is essential to ensure that the measurement systems and methodologies perform as expected. A measurement control program also allows for a determination of the level of confidence in the accounting values.

Analysis of Tank 38H (HTF-38-15-47, 49) and Tank 43H (HTF-43-15-51, 53) surface and subsurface supernatant samples in support of enrichment and corrosion control programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oji, L. N.

This report provides the results of analyses on Tanks 38H and 43H surface and subsurface supernatant liquid samples in support of the Enrichment Control Program (ECP) and the Corrosion Control Program (CCP).

12 CFR Appendix B to Part 741 - Guidance for an Interest Rate Risk Policy and an Effective Program

Code of Federal Regulations, 2013 CFR

2013-01-01

... Measurement Methods C. Components of IRR Measurement Methods V. Internal Controls VI. Decision-Making Informed... effective IRR management program identifies, measures, monitors, and controls IRR and is central to safe and... critical to the control of IRR exposure. All FICUs required to have an IRR policy and program should...

12 CFR Appendix B to Part 741 - Guidance for an Interest Rate Risk Policy and an Effective Program

Code of Federal Regulations, 2014 CFR

2014-01-01

... Measurement Methods C. Components of IRR Measurement Methods V. Internal Controls VI. Decision-Making Informed... effective IRR management program identifies, measures, monitors, and controls IRR and is central to safe and... critical to the control of IRR exposure. All FICUs required to have an IRR policy and program should...

50 CFR 648.262 - Effort-control program for red crab limited access vessels.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Effort-control program for red crab... UNITED STATES Management Measures for the Atlantic Deep-Sea Red Crab Fishery § 648.262 Effort-control program for red crab limited access vessels. (a) General. A vessel issued a limited access red crab permit...

76 FR 12758 - Comment Request for Information Collection for the Evaluation of the Reintegration of Ex...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... the program (60 percent) or the control (40 percent) group. The evaluation includes: An implementation... participants to either the program group, which was offered program services, or the control group, which was... control groups (the latter could access non-RExO services) as well as variations across grantees. By...

76 FR 77554 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Growing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... applicants to Project GATE were randomly assigned to either a program group or a control group. The project... telephone survey of participants and control group members was conducted to collect three waves of data at... program group or a control group. Members of the program group are eligible to receive GATE II services...